Abstract:Aim and Background The beneficial effect of estrogen on atherosclerosis and related cardiovascular disease has been recognized, however there were obvious adverse side effect recently. This controversy were continued more intensely. We found a new phytoestrogen α-Zearalanol (ZAL). Our lab first brought ZAL into medical research field to study its antiatheorsclewsis effect. To examine the effect on atherosclerosis (As) development and serum lipid prolife, and in comparison with estrogen, in order to provide a basic materials for future study. Methods Sixty adult female New-Zealand rabbits were divided into 7 groups: normal control (NC)group (n=6), sham-operated (SO) group (n=8),high-cholesterol control(HCC) group (n=10), small dose ZAL (SDZ) group (n=8), medium dose ZAL (MDZ) group (n=10),large dose ZAL (LDZ) group (n= [WT5”BZ]8), 17β-estrogen (E₂) group (n=10). All groups except NC group and SO group were treated with oophoretomy; all groups except NC group were fed with high-cholesterol for 12 weeks. At week 0, 4, 8, and 12,the serum lipid TC, TG, HDLC, LDLC, apolipoprotein Al and B were measured. At feeding cholesterol week 12 the area of aortic intima lipid plagues to total area of aortic intima were evaluated by scanner and the pathologic changes were observed. Results The ratio of area of aortic lipid plaque to total area of aortic intima in NC group was 0.02±0.003, in SO group was 0.42±0.15, in HCC group was 0.67±0.23, in SDZ group was 0.61±0.13, in MDZ group was 0.10±0.06, in LDZ group was 0.32±0.10, in E₂ group was 0.12±0.11 (SO group, MDZ group, LDZ group, and E₂ group four groups are compared with HCC group,p<0.01). The serum contents of TC, TG, LDLC, apolipoprotein B in HCC group was siginificantly increased compared with the SO group, while those in MDZ groups, LDZ group, and E₂ group, were significantly decreased compared with HCC group. The pathologic changes showed in NC group intact endothelial cell. In HCC group it showed severe endothelial cell damaging and falling off, liquid like necrosis, obvious outward shifting of intimal elastic layer, a large amount of foam cell and lipid plaque, necrosis and calcification. In SO group, in MDZ groups, LDZ group, and E₂ group, aforementioned pathological atteration were significantly attenuated. Conclusion Administration of ZAL can decrease the area of aortic lipid plaque and markedly reduce the pathological changes and participate improvement and regulation of disturbance of lipid metabolism including the degree on hyperlipidemia. Phytoestrogen ZAL has a potentially importment antiatherogen effect. Analogous to that observed with 17β-estrogen in this model.

Abstract:Aim To investigate whether transient myocardial ischemia might cause protein aggregation, and to observe whether heat shock pretreatment and ischemic preconditioning could alleviate protein aggregation. Methods Myocardial ischemial-reperfusion injury model was prepared by ligation of left descending anterior coronary artery for 15 minutes then released for various durations in rats. Protein aggregates induced by ischemia-reperfusion injury in cardiomyocytes were observed by using ethanolic phosphotungstic acid (EPTA) electron microscopy (EM). The influence of heat shock protein 70 (HSP70) and αB-crystallin on above protein damage was further investigated by immunoelectron microscopy. Results ①Myocardial ischemia-reperfusion resulted in protein aggregation, which appeared at 30 min of reperfusion, peaked at 4 h of reperfusion, decreased from 24 h of reperfusion and restored to normal at 72 h of reperfusion after 15 min of ischemia. ②Heat shock pretreatment (rectal temperature 42℃ for 15 min then recovery for 24 h) and ischemic preconditioning (ischemia for 3 min then reperfusion for 10 min ) significantly decreased myocardial protein aggregates induced by 15 min of ischemia and 4 h of reperfusion and facilitated the restoration of myocardial protein damage. ③HSPs played key roles in the myocardial protection of heat shock pretreatment and ischemic preconditioning. In the present study, we found that HSP70 and αB-cystallin co-localized with protein aggregates in heat shock pretreatment and ischemic preconditioning groups. Conclusion This study, for the first time, demonstrated the formation, intracellular distribution and dynamic patterns of myocardial protein aggregates induced by ischemia-reperfusion injury, and found that heat shock pretreatment and ischemic preconditioning alleviated the formation of myocardial protein aggregates.

Abstract:Aim To study the expression level of retinoblastoma (Rb) and CD36 in U937 cells treated with oxidized low density lipoprotein(ox-LDL) or pretreated with exogenous Rb gene. Methods Human myeloid leukemia U937 cells were incubated with ox-LDL(80 mg/L) at 0 h,12 h,24 h and 48 h after ox-LDL loaded respectively. CD36 and Rb gene expression were detected by RT-PCR and flow cytometric analysis(FCA). Results RT-PCR and FCA results showed that the expression level of Rb was downregulated and the expression level of CD36 upregulated from 0h to 48h induced by ox-LDL. While after being transfected by exogenous Rb gene via a recombinant adenovirus vector, the expression level of Rb was upregulated and the expression level of CD36 downregulated with a time-dependent manner. Conclusions Ox-LDL could downregulate the expression level of Rb mRNA and protein, and upregulate that of CD36. Introduction of exogenous Rb gene could downregulate expression of CD36 of U937 cells.

Abstract:Aim To study the effects of simvastatin,probucol and captopril on regression and stabilization of atherosclerosis, and to explore the expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1). Methods 50 rabbits were induced to atherosclerosis by feeding cholesterol and then treated with simvastatin, probucol, captopril respectively for 12 weeks. The tissues of abdominal aorta were studied by reverse transcription polymerase chain reaction (RT-PCR), pathology and immunohistochemistry staining. Results The lipids were decreased in the drug-therapy groups significantly (p<0.05), especially in probucol and simvastatin groups. The atherosclerosis regressed significantly in the drug-therapy groups (p<0.05), and simvastatin had the best result. The expression of mRNA level of collagen Ⅰ, MMP-1 and TIMP-1 was decreased in drug-therapy groups, but was statistically significant only in the probucol group (p<0.01). Conclusion Simvastatin, probucol and captopril could regress the atherosclerosis and stabilize the plaque by reducing the expression of MMP-1.

Abstract:Aim To examine the effects of monocyte-endothelium interaction on the secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and macrophage colony-stimulating factor (M-CSF), and to explore the functions of adhesion molecules in the process. Methods Monocytes and endothelial cells were cultured alone or cocultured to form different cell culture conditions. Pretreatments with monoclonal antibody of human intercelluar adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelium selectin (E-selectin) were carried out in cocultured groups. The levels of TNF-α, IL-1β and M-CSF in culture medium were determined by enzyme linked immune sandwich assay technique. Results There was no secretion of TNF-α, IL-1β and M-CSF observed in monocytes or endothelial cells culture alone. The secretion of three types of cytokines increased significantly when two types of cells were cocultured (p<0.05). Direct contact between monocytes and endothelial cells played an important mediated role in the process. E-selectin played the principal role in activating the secretion of TNF-α and IL-1β, and ICAM-1 was the most principal adhesion molecule to mediate the secretion of M-CSF. Conclusion The adhesion of monocytes to endothelial cells can activate certain signal transduction, resulting in significantly increased secretion of TNF-α,IL-1β and M-CSF. Adhesion molecules play a pivotal role in the process.

Abstract:Aim To observe the Xue Zhi Kang’s (XZK) effect on blood lipid and atherosclerosis (As) of apolipoprotein E deficient (Apo E°)mice. Methods Six week old Apo E° mice were assigned randomly into hyperlipidemia group (fed with saline) and XZK group (fed with XZK). Six week old heathy mice (C57BL/6J mice) were the normal group (fed with saline ). They were treated for 14 weeks, then total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLC) and high density lipoprotein cholesterol (HDLC) were determined, and the aortas were preceded in the formalin for morphological research and photograph analysis. Results TC, TG and LDLC of hyperlipidemia group were significantly higher than those of the normal group; TC, TG and LDLC of XZK group were definitely lower than those of hyperlipidemia group (p<0.05 ). The photography analysis showed that the lesion of hyperlipidemia group was very obvious. Compared with normal group, the total atheromatous plaque square increased obviously (p<0.05 ). Morphological reseach showed that As lesions were found in aortas of hyperlipidemia group and XZK group. While As lesions of hyperlipidemia group were more serious than those of XZK group, and no As lesions were found in normal group. Conclusion Xue Zhi Kang can lower the serum cholesterol and relieve the As lesions of the Apo E° mice.

Abstract:Aim To observe the occurrence and the morphological manifestation of atherosclerotic lesions in apolipoprotein E gene knockout (ApoE -/-) mice. Explore the relationship between lesion formation and adventitial inflammation. Methods The successive sections of the hearts of 60 and 112 weeks old ApoE -/- mice were made, then stained by Movat method. Trailled all the trunks and intra-myocardial small branches of coronary arteries for finding the lesions, and analyzed the relationship between lesion distribution and adventitial inflammation. The aseptic adventitial inflammation of the femoral artery in C57BL/6 mice were duplicated, detected the expression of adhesive molecules. Results There were extending lesions in the trunks of coronary artery, which extended directly from the aorta. There were in situ lesions in the branches of the trunks (including intra-myocardial small branches). There were inflammatory cells aggregation at the adventitia with the lesions at the corresponding intima. The infiltrating area of inflammatory cells was much larger than the area of lesion at intima. Some positions with inflammatory infiltration in adventitia could be seen without lesion at corresponding intima. All the in situ lesions were arised within ventricular muscle, most of the large in situ lesions appeared in the left ventricular wall. ICAM-1, VCAM-1 and adhesion of white blood cells could be seen at the intima of femoral artery in the mice with experimental aseptic adventitial inflammation. Conclusions The adventitial inflammation is one of the predisposing factors for the formation of lesions within the coronary artery.

Abstract:Aim To observe the occurrence and the morphological manifestation of atherosclerotic lesions in apolipoprotein E gene knockout (ApoE -/-) mice. Explore the relationship between lesion formation and adventitial inflammation. Methods The successive sections of the hearts of 60 and 112 weeks old ApoE -/- mice were made, then stained by Movat method. Trailled all the trunks and intra-myocardial small branches of coronary arteries for finding the lesions, and analyzed the relationship between lesion distribution and adventitial inflammation. The aseptic adventitial inflammation of the femoral artery in C57BL/6 mice were duplicated, detected the expression of adhesive molecules. Results There were extending lesions in the trunks of coronary artery, which extended directly from the aorta. There were in situ lesions in the branches of the trunks (including intra-myocardial small branches). There were inflammatory cells aggregation at the adventitia with the lesions at the corresponding intima. The infiltrating area of inflammatory cells was much larger than the area of lesion at intima. Some positions with inflammatory infiltration in adventitia could be seen without lesion at corresponding intima. All the in situ lesions were arised within ventricular muscle, most of the large in situ lesions appeared in the left ventricular wall. ICAM-1, VCAM-1 and adhesion of white blood cells could be seen at the intima of femoral artery in the mice with experimental aseptic adventitial inflammation. Conclusions The adventitial inflammation is one of the predisposing factors for the formation of lesions within the coronary artery.

Abstract:Aim To explore the effects of Xuezhi Kang on cholesterol and functions of endothelial cells in cholesterolfed rabbits. Methods The effects of Xuezhi Kang [0.8 g/(kg·d)] on the functions of endothelial cell during the progression of atherosclerosis were investigated in rabbits fed with 1.5% cholesterol diet in this study. 30 New Zealand white rabbits were divided into three groups (control group, hypercholesterol group and Xuezhi Kang group) during the 12 weeks experiment. Serum lipids, nitrous oxide (NO) and plasma endothelin-1 (ET-1), thromboxane (TX),6-keto-prostaglandin-F 1α (6-keto-PGF 1α) concentrations and histopathological changes of endothelial cells were followed. Results Serum total cholesterol, low density lipoprotein cholesterol, triglyceride, plasma ET-1 concentrations and the ratio of TX/6-keto-PGF 1α in plasma decreased and serum NO level increased in Xuezhi Kang group as compared with those of hypercholesterol group (p<0.05). The area of lipid deposition on the intimal surface of the aorta and coronary arteries was reduced and the ultrastructural injuries of endothelial cells were milder in Xuezhi Kang group. Conclusion Xuezhi Kang had antiatherogenic properties and the protection to the functions of vascular endothelial cells which might be involved in the mechanisms of Xuezhi Kang against atherosclerosis.

Abstract:Aim To elucidate the effect of estradiol on the endothelium of rabbits iliac artery after balloon injury. Methods 28 female rabbits were randomly divided into four groups. All rabbits were ovariectomized. The endothelial denudation was performed by utilizing the balloon of percutaneous transluminal coronary angioplasty in rabbit right iliac artety. 2 weeks and 4 weeks after balloon injury of the artery, serum levels of estradiol were measured and reendotheliums were assessed by IBAS 2000 morphometric system. The functions of endothelium were tested by measuring the nitric oxide (NO) levels of injured artery. Results Serum levels of estradiol significantly elevated in estrogen treated groups compared with the control groups(p<0.01). The reendothelialization was more accelerated in estrogen treated groups(p<0.05), the corelationship between them is strikingly. The enhanced NO release were observed in estrogen treated groups(p<0.05). Conclusions Estrogen can accelerate reendothelialization after balloon injury and protect the function of injured vascular endothelial cells, so as to have the effects of antiatherosclerosis.

Abstract:Aim To investigate the endothelial function and platelet activation during myocardial ischemia-reperfusion injury and the protective effect of magnesium. Methods Thirty-two rabbits were randomly divided into four groups. In control group the left anterior descending coronary artery (LAD) was falsely ligated. In ischemia group the LAD was ligated. Rabbits in reperfusion group and therapy group underwent 0.5 h of LAD occlusion and 4 h of reperfusion. After LAD ligation rabbits in therapy group were intravenously given magnesium sulfate and rabbits in the rest groups were given 0.9% sodium chloride. The level of plasma Mg 2+, nitric oxide (NO) and the number of alpha-granule membrane protein-140 (GMP-140) molecule on platelet surface were measured before LAD ligation and after ischemia for 0.5 h, reperfusion for 1 h and 4 h. Results ①The plasma concentrations of Mg 2+, NO and the number of GMP-140 molecule on the platelet surface in control group were of no statistical difference before and after false LAD ligation (p>0.05); ②The level of Mg 2+, NO were significantly decreased and the number of GMP-140 molecule on platelet surface was increased after myocardial ischemia/ischemia-reperfusion in ischemia group, reperfusion group compared with those before LAD ligation and those at the same time in control group (p<0.05); ③The level of Mg 2+,NO was increased and GMP-140 was decreased in therapy group compared with those in ischemia group and reperfusion group (p<0.05). Conclusions It suggests that there is endothelial dysfunction and platelet activation during ischemia-reperfusion. Sulfate magnesium might be useful in protecting endothelium and inhibiting platelet activation.

Abstract:Aim The study was designed to examine the relationship between polymorphism at the apolipoproteinlipoprotein E gene and the risk of coronary artery disease (CAD). Furthermore, the association of the polymorphism with the classical risk factors was analyzed. Methods A total of 124 patients with angiographically verified CAD or myocardial infarction were prospectively evaluated. Data referring to hypertension, diabetes and tobacco consumption were recorded. The plasma levels of total cholesterol, HDL cholesterol, apolipoproteinlipoprotein AI and B and triglycerides were determined. DNA was obtained from the 124 patients and from 70 controls. In order to determine the apolipoproteinlipoprotein E genotypes, DNA was PCR amplified and digested with HhaI. Results The frequency of the ε2, ε3 and ε4 are 0.155±0.300, 0.648±0.342, and 0.197±0.246 in Uygur population and 0.081±0.196, 0.772±0.315, and 0.146±0.237 in Han population respectively. The frequency of the ε2, ε3 and ε4 are 0.060±0.198, 0.758±0.302, and 0.182±0.250 in the patient group and 0.193±0.286, 0.671±0.370, and 0.136±0.224 in the control group respectively. ε2 frequency of Uygur' patient and control are 0.050±0.221 and 0.290±0.336. Serum LDL cholesterol, TC and TG values tended to decrease from the apolipoproteinlipoprotein E-4 phenotypes to apolipoprotein E-2 phenotypes. Deletion polymorphism of ε2 compared with common risk factors for CAD, its risk ratio (RR) is 4.38. Conclusion These studies showed that the apolipoprotein E phenotype distribution in Uygur population differed significantly from Han population in Xinjiang. CAD patients have significantly lower ε2 allele than controls especially in Uygur population. Deletion of ε2 may be a risk factor for CAD.

Abstract:Aim To study the trend of changes in serum total cholesterol (TC) levels of governmental and institutional staffs of urban districts in Beijing during 1981-2001. Methods A total of 47 434 TC data were collected after annual physical examination, and analyzed statistically according to different sex, age and years. Serum TC measurements fulfilled the quality criteria of lipid standardization. Results ① TC level increased evidently in the period 1981 to 1988, and reached to the higher level at 1990, but was lower in 2001 than 1991. The age adjusted mean TC level during 1981～1990 increased by 0.73 mmol/L (28 mg/dL) in males, and 0.62 mmol/L (24 mg/dL) in females, but decreased by 0.21 and 0.23 mmol/L (8 and 9 mg/dL) respectively in males and females in the year 2001. ② TC increased with age in both sexes, however, the degree of increase was different in males and females. The elevation of TC level with age was more significant in young males than females, but was much more marked in females after middle age. From 40～49 to 50～59 age groups, the average TC increase was 3% in males, and 14% in females. It hardly increased after age 60 in both sexes. The total increase in TC from young age to elderly was 20% in males and 35% in females. Thus TC level in males was higher before age 50, but lower than in females after age 50. ③The prevalence rate of age standardized hypercholesteroleria [TC≥5.17mmol/L(200 mg/dL)、≥5.7 mmol/L(220 mg/dL)and ≥6.2 mmol/L(240 mg/dL)] was doubled approximately in 1991 compared with 1985, but somewhat lowered in 2001. ④The age adjusted mean TC is 4.86 mmol/L (188 mg/dL, male) and 4.78 mmol/L(185 mg/dL, female) with prevalence rate of age standardized high TC about 20% (≥5.7 mmol/L) or 10% (≥6.2 mmol/L) at present. Conclusion There was marked increase in prevalence rate of high TC in 1980′s, no more increase in 1990′s, but a little decrease in 2001.

Abstract:Aim To study the effects of carotid atherosclerosis on activated patelets and the relation with acute cerebral infarction. Methods Colour doppler flow imaging (CDFI) was used to assess carotid atherosclerosis and flow cytometry was employed to detect CD62p and CD63 expression on circulating platelet in 115 patients with acute cerebral infarction and 30 controls. Results The plaques of internal carotid artery (ICA) were significantly increased in patients with acute cerebral infarction than those in controls. 68.75% of left or right hemispheric infarctions was ipslateral to their plaques and 58.47% of the patients with bilateral hemispheric infarction had bilateral ICA plaques. The blood flow velocites were significantly increased in the throat of stenosis of ICA plaques. CD62p and CD63 expression on platelet were significantly higher in patients with ICA plaques than those in normal carotid controls, the positive percentages and fluorescence intensity of CD62p and CD63 were 4.72%±4.52%, 5.38%±3.73% and 1.50±0.26, 1.38±0.14 respectively in subjects with unilateral plaques and were 7.72%±4.96%, 6.78%±4.02% and 1.59±0.37, 1.41±0.18 respectively in subjects with bilateral plaques. Rates of platelet activation in the patients with brain infarction was higher than those in the controls and was related to the severity of carotid atherosclerosis. Conclusions The plaques of carotid atherosclerosis result in the complex patterns of high wall shear stress followed by low wall shear stress. Circulating platelets can be activated under the complex patterns of shear stress, which surgests shear-inducd platelet activation might play a pathogenetic role in onset of acute cerebral infarction.

Abstract:Aim To compare the immediate and long-term outcomes of coronary stenting for total occlusions with nonocclusive stenoses. Methods A total of 516 consecutive patients (687 lesions) underwent coronary stenting. The study population was divided into total occlusion group (TO group, 142 patients with 160 lesions) and non-occlusion group (NO group, 374 patients with 527 lesions). The immediate and long-term angiographic and clinical outcomes were assessed. Results There was no difference in postprocedure minimum lumen diameter (3.12±0.51 vs. 3.13±0.54 mm, p>0.05) between TO and NO groups. There was no difference in incidence of clinical complications between the two groups. A total of 27.8% of patients in TO group and 23.7% of lesions in NO group occurred restenosis (p>0.05). Clinical events occurred in 25.2% of patients in TO group compared with 22.7% in NO group (p>0.05). Conclusions The immediate and long-term outcomes of coronary stenting for total occlusions are comparable to that for nonocclusive stenoses.

Abstract:Aim To evaluate the effect of aspirin time-release on the incidence of cerebro-cardiovascular accidents in hypertensive or coronary patients, and to access the influence of age, blood pressure, sex, smoking, et al. Methods This study was an opening, multicenter, randomized, and controlled clinical research. 2 551 patients were enrolled and 2 430 patients had completed the study finally. 1 264 patients were assigned to aspirin time-release 50 mg/d～100 mg/d besides antihypertensive treatment or the routine therapy on coronary heart disease except anticoagulant. The other 1 166 control patients received only routine therapy. Results The study observed that active treatment obviously reduced the incidence of cerebro-cardiovascular accidents (p<0.05 or p<0.001). To compare with the controlled group, the RR (95%) of cerebro-cardiovascular accidents in treated group was 0.341 (0.254～0.460), and the RR of cerebral infarction, cerebral hemorrhage, myocardial infarction was 0.379 (0.258～0.559), 0.203 (0.106～0.388), 0.335 (0.107～1.051) respectively. Furthermore, the RR of death caused by cerebro-cardiovascular accidents was 0.148 (0.052～0.423). After stratifying of blood pressure, the RR of cerebro-cardiovascular accidents was higher in the people with high blood pressure. Conclusions The active therapy with low-dose aspirin could significantly reduce the incidence of cerebro-cardiovascular accidents in high risk group. It is beneficial to control the high risk factors such as blood pressure, smoking, drinking for hypertensive or coronary patients.

Abstract:Aim To investigate the relationship of variable number of tandem repeat(VNTR) polymorphism in intron 2 of interleukin-1 receptor antagonist(IL-1Ra)gene and serum IL-1Ra levels with coronary heart disease. Methods 245 coronary heart disease patients and 236 normal subjects were recruited in the study. Their VNTR polymorphisms of IL-1Ra gene were analyzed using polymerase chain reaction method and their serum IL-1Ra levels were measured using enzyme-linked immunosorbent assay. Results There were four kinds of genotype: Ⅰ/Ⅰ, Ⅰ/Ⅱ, Ⅰ/Ⅳ and Ⅱ/Ⅱ. The frequencies of the four genotypes were as follows:Ⅰ/Ⅰ,88. 6%;Ⅰ/Ⅱ,9.8%;Ⅰ/Ⅳ,1.2%;Ⅱ/Ⅱ,0.4% in coronary heart disease patients andⅠ/Ⅰ,80.1%;Ⅰ/Ⅱ,16.9%;Ⅰ/Ⅳ,2.1%;Ⅱ/Ⅱ,0.9% in normal subjects, respectively. The frequency of alleleⅡ was significantly lower in coronary heart disease patients, than that in normal controls(5.3% and 9.3%, respectively),which is more significant in myocardial infarction patients and angina patients(4.3% and 15.6%, respectively). In coronary heart disease patients, the serum IL-1Ra levels in allele Ⅱ carriers were significantly higher than in no allele Ⅱcarriers. Conclusion The VNTR polymorphism of IL-1Ra gene may affect serum IL-1Ra levels, and may play a protective role in the development of coronary heart disease.

Abstract:Aim To investigate the effect of the new potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, atorvastatin, on platelet aggregation in Chinese patients with hypercholesterolaemia. Methods Four agonists to induce platelet aggregation in whole blood were tested in normal subjects. The platelets showed good response to collagen in vitro but poor response to adenosine diphosphate (ADP) and adrenaline. The aggregation response to collagen 1.0 and 2.5 mg/L was assessed in 30 patients who had been receiving atorvastatin for 16 weeks, titrated at 4-week intervals through 10, 20, 40 and 80 mg daily until target low density lipoprotein cholesterol (LDLC) levels were achieved. Results The tests were repeated 4-weeks after stopping therapy. Withdrawal of atorvastatin resulted in the expected increases (all p<0.001) in total cholesterol (TC), triglycerides (TG) and LDLC from 5.0±1.1, 2.2±3.3, 3.0±1.0 mmol/L to 9.0±3.1, 5.0±12.4, 6.8±1.5 mmol/L respectively without significant change in high density lipoprotein cholesterol. Platelet count and volume remained unchanged after cessation of therapy and the slope and magnitude of the platelet aggregation curve in response to collagen 1.0 mg/L was unchanged whereas the amplitude of the response to collagen 2.5 mg/L increased from 17.1±4.6 Ω to 19.0±3.1 Ω without change in slope. Conclusion We concluded that atorvastatin treatment produced large reductions in TC, LDLC and TG, and that the only change seen in whole blood platelet aggregation was a small but significant reduction in the amplitude of the response to collagen 2.5 mg/L.

Abstract:Aim To examine the relationship between glycopropean complex of activated platelet (PAC-1) and lipid metabolic disturbance in cases of type 2 diabetes mellitus (DM). Methods One hundred and twenty two patients with DM (type 2) were divided into lipid metabolic disturbance group (62 cases) and normal lipid metabolism group (58 cases). 25 normals were selected as the control. Flow-cytometry was used to detect the PAC-1 level and therefore the deference between the two groups was analysed. The correlation between triglyceride (TG), high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) and PAC-1 was also evaluated. Results The PAC-1 level in type 2 DM cases was higher than that in control subjects. It was also markedly higher in abnormal lipid metabolic cases than that in normal lipid metabolic cases. LDLC correlated positively with PAC-1 (r=0.64, p<0.05). Conclusion Abnormal lipid metabolism is the main factor resulting in a high PAC-1 level.

Abstract:Aim To study the relationship between plasma creatinine and the severity of coronary artery stenosis in patients with diabetes mellitus. Methods Ninty-one patients with diabetes mellitus underwent coronary angiograhy were evaluated with plasma creatinine before the procedures; in 55 patients with coronary heart disease (CHD), the relationships between plasma creatinine and the Leaman coronary artery score (LCAS) were assessed. Results The plasma creatinine of CHD group (114.0±28.6 μmol/L) was remarkably higher than that (80.5±25.2 μmol/L) in no-CHD group (p<0.01). In CHD group, the plasma creatinine had significantly positive correlation to Leaman coronary artery score (r=0.64, p<0.01), in the sub-group with hypertension (diabetes mellitus + hypertension), creatinine had Singificantly positive correlation to LCAS (r=0.81, p<0.01). Conclusion The plasma creatinine may be used to assess the severity of coronary artery stenosis in the patients with diabetes mellitus.

Abstract:Aim To investigate pathogenesis of atherosclerosis,three methods for establishment of rat animal model were compared. Methods Three different methods,including high lipid only, high lipid+ Vitamin D overload, and high lipid+ Vitamin D overload+ endothelium injure, were used for inducing atherosclerosis in rats. After 90 days, serum lipid, serum calcium, morphology change of thoracic aorta were determined,and immunohistochemical assay of macrophage and (-smooth muscle actin were performed. Results The levels of serum total cholesterol (TC),triglyceride (TG),LDLC in three groups(hyperlipidemia group,hyperlipidemia + vitamin D3 group,and hyperlipidemia + vitamin D3 + endothelium denudate group)were obviously higher than those in control group (p<0.01). The levels of serum calcium in two groups(hyperlipidemia + vitamin D3 group and hyperlipidemia + vitamin D3 + endothelium denudate group)were also obviously higher than those in control group and hyperlipidemia group (p<0.01). Compared with control group,there were thicker intima,thinner media in hyperlipidemia + vitamin D3 group and hyperlipidemia + vitamin D3 + endothelium denudate group(p<0.05 and p<0.01). By immunohistochemistry,the CD68 positive level were low in hyperlipidemia group and hyperlipidemia + vitamin D3 group,and high in hyperlipidemia + vitamin D3 + endothelium denudate group. The α-actin positive level in intima is thick in hyperlipidemia + vitamin D3 group,thin in hyperlipidemia + vitamin D3 + endothelium denudate group.The rats treated with high lipid only showed hyperlipidemia without As lesion ;the rats treated with high lipid+ Vitamin D overload showed fibrous plaque; the typical mature atheromatous plaques were presented in the rats treated with high lipid+ Vitamin D overload+ endothelium injure creates mature atheromatous plaque. Conclusions Rat can be used as a ideal model for research atherosclerosis.The mature atheromatous plaque may created by high lipid + Vitamin D overload and endothelium injure.

Abstract:Aim A method has been developed for the rapid isolation of platelet membrane glycoproteins (GP) Ⅱ_b and Ⅲ_a. Methods The GP Ⅱ_b/Ⅲ_a complex was purified with concanavalin A-sepharose, heparin-sepharose and sephacryl S-300HR chromatography. Results The GP Ⅱ_b/Ⅲ_a complex, GP Ⅱ_b is composed of two disulfide-linked chains, a heavy chain of 125 kDa, called GPⅡ_bα, and a light chain of 23 kDa, called GP Ⅱ_bβ, in reduced conditions. The GP Ⅲ_a is a single polypeptide of 108 kDa in reduced conditions, or 95 kDa in nonreduced conditions. Conclusions Concanavalin A affinity chromatography was used to purify a platelet glycoprotein fraction. The concanavalin A-retained glycoproteins were eluted and adsorbed with a heparin-sepharose column to remove a major contaminant, thrombospondin. Sephacryl S-300 gel filtration was used as the final purification step to remove most fibrinogen and low-molecular-weight contaminants. The GP Ⅱ_b/Ⅲ_a complex can be used for the development of its biological products and further study.

Abstract:Aim To study the relationship between the expression status of apolipoprotein E gene and children health,developed a new method for the quantification of apolipoprotein E mRNA in human monocyte-derived macrophages. Methods 10 mL venous blood was obtained from 26 health children.The mononuclear cells were isolated.Total RNA from the monocytes was extracted.Apolipoprotein E gene express were determined by reverse transcription-polymerase chain reaction. After synthesis of the internal apolipoprotein E DNA standard,we amplified internal standard DNA and cDNA of samples studied. Quantification of apolipoprotein E gene express was calculated. Results Apolipoprotein E mRNA was 0.37±0.15 mol/mol GAPDH mRNA in health children. Conclusions The competitive reverse transcription- polymerase chain reaction was a rapid,simple,sensitive method to study expression of apolipoprotein E gene. This method might be a valuable tool to assess apolipoprotein E gene expression in human disease.