Abstract:Aim To explore the effect of astragalus polysaccharides （APS） on myocardial hypertrophy in rats induced by isoproterenol （ISO）. Methods 15 mg/（kg·d） ISO were used as myocardial hypertrophy models by intraperitoneally injection. 60 SD rats were randomly assigned to six groups, 10 rats for each group: the control group, ISO group, ISO＋APS 200 mg/（kg·d） group, ISO＋APS 400 mg/（kg·d） group, ISO＋APS 800 mg/（kg·d） group and ISO＋propranolol 40 mg/（kg·d） group. Administered groups were continually intraperitoneally injected administration for 3 weeks, and ISO were intraperitoneally injected as long as 2 weeks in the day after that. After 3 weeks, at the end of the treatment period, hemodynamic parameters were observed, and pathological section by HE staining. The expression of free fatty acid （FFA）, ATP, ADP, AMP were quantified by ELISA. The expression of atrial natriuretic factor （ANF）, PGC-1α mRNA were determined by RT-PCR, the expression of PGC-1α protein were determined by Western blot in the tissue. Results Compared with control group, ISO group markedly elevated HMI, LVMI, LVEDP level and decreased LVSP level, meanwhile the expression of ANF mRNA were increased and the expressions of PGC-1α mRNA and protein decreased. Compared with ISO group, the APS for different dose groups dependently improved hemodynamic parameters, ATP/AMP and ATP/ADP ratio and PGC-1α mRNA and protein expressions. Conclusions APS can improve cardiac hypertrophy induced by ISO, which maybe improve energy metabolism by PGC-1α.

Abstract:Aim To investigate the effect of telmisartan on rabbit apoptotic cardiomyocytes underwent ischemia/reperfusion(I/R) injury. Methods 48 Healthy male New Zealand white rabbits were randomly divided into six groups(n=8): sham operation group,I/R model group,GW9662 group,telmisartan group,telmisartan+GW9662 group,candesartan group.After intragastric administration for 2 weeks,the left anterior descending(LAD) coronary artery was occluded for 60 minutes followed by 360 minutes reperfusion to induce ischemia/reperfuion injury.The concentration of angiotensinⅡ in myocardium was analyzed by radioimmunoassay and the intracellular free calcium concentration was measured by dual wavelength fluorophotometry.Then,protein expression of peroxisome proliferator activated receptor-γ(PPARγ) was detected by Western blot.In addition,apoptosis was detected by transmission electron microscope and by TUNEL staining. Results Compared with sham operation group,the concentration of angiotensinⅡin myocardium was significantly increased in I/R model group,GW9662 group,telmisartan group,telmisartan+GW9662 group,and candesartan group(P<0.01).And,the expression of PPARγ was higher in telmisartan group than that in other groups(P<0.01).Interestingly,telmisartan,telmisartan+GW9662 and candesartan inhibited the morphological chan ges of apoptotic cardiomyocytes,which was induced by myocardial ischemia/reperfusion,by condensing chromatin clumps against the nuclear envelope and presentation of apoptotic body.When compared with I/R model group,the intracellular free calcium concentration and apoptosis index were significantly reduced in telmisartan group,telmisartan+GW9662 group and candesartan group(P<0.01).Among them,apoptosis index was lowest in telmisartan group(P<0.01). Conclusion Telmisartan could reduce myocardial apoptosis by blocking the angiotensinⅡreceptor and up-regulating the expression of PPARγ in the rabbit I/R model.

Abstract:Aim To observe the intimal hyperplasia of peroxisome proliferator activated receptor-γ(PPARγ) agonist rosiglitazone on vein graft. Methods Jugular veins graft model of rats were established.16 rats were divided into rosiglitazone group and model group randomly(8 in each group),rosiglitazone was used in rosiglitazone group.The weight of rats,hyperplasia endomembrane on light microscope,RT-PCR result of electrophoresis were observed after six weeks. Results The weight in model group(521.6±22.3 g) was increased compared with in rosiglitazone group(457.3±25.3 g,P><0.05).Hyperplasia endomembrane in rosiglitazone group was 25.99±3.31 μm and 35.28±5.76 μm in model group compared with normal vein.Expression of PPARγ mRNA in rosiglitazone group(1.12±0.28) was increased compared with model group(0.68±0.20,P><0.05). Conclusion PPARγ agonist rosiglitazone alleviates intimal hyperplasia of vein graft after autologous transplantation in rats.

Abstract:Aim To investigate the role of peroxisome proliferator activated receptor-γ (PPAR-γ) in the regulation of matrix metalloproteinases (MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression by peripheral blood monocyte derived macrophages (MDM) in acute coronary syndrome (ACS) patients. Methods MDM were from patients with ACS and controls have been assigned to different subgroups and incubated by different concentrations of rosiglitazone. The concentrations of MMP-9 and TIMP-1 in the supernate of MDM and the expression strength of PPAR-γ,MMP-9 and TIMP-1 mRNA in MDM were analysed and compared between ACS group and control group,and among the different concentrations of rosiglitazone intervention subgroups. Results After rosiglitazone interventing,either in ACS group or in control group,PPAR-γ mRNA expression were significantly upward,and there were a positive correlation between the expression strength and rosiglitazone intervention concentration; both the MMP-9 concentration in the supernate and the expression strength of MMP-9 mRNA were descended,and there were negative correlation between the extent of its descent in the ACS group and rosiglitazone concentration. There was no significant change in TIMP-1 concentration in the supernate of MDM and TIMP-1mRNA expression after rosiglitazone interventing. Conclusion MDM had endogenous PPAR-γ receptor,and it could be activated by rosiglitazone. Rosiglitazone intervention significantly increased the expression of PPAR-γ of MDM,reduced the expression of MMP-9,particularly in the ACS group. TIMP-1 expression was not affected. There may be impact of stablizing atherosclerotic plaque.

Abstract:Aim To evaluate the possible association between PPARγ2 gene Pro12Ala polymorphism and type 2 diabetes mellitus in a population-based study in Weifang Han population. Methods Genomic DNA was extracted from peripheral blood leucocytes of 170 patients with type 2 diabetes mellitus and 54 normal subjects. The Prol2Ala polymorphism was screened using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The frequencies of Pro allele and Ala allele were 0.9487 and 0.0513 respectively in 224 subjects from Han people of Weifang Chinese. The Ala allele frequency in the control group and type 2 diabetes mellitus group were 0.093 and 0.041 respectively. The Ala allele frequency in type 2 diabetes mellitus was significantly lower than that in the control group (P=0.039). Conclusion PPARγ2 gene Prol2Ala polymorphism is associated with the incidence of type 2 diabetes mellitus in Han people of Weifang Chinese. The Ala allele confers modest protection against the onset of type 2 diabetes mellitus.

Abstract:Aim To explore whether homocysteine thiolactone(HTL)-induced vascular endothelial dysfunctions relate to activation of peroxisome proliferator activated receptor-γ(PPARγ).Methods The endothelium-dependent relaxation(EDR) and non-endothelium-dependent relaxation(n-EDR) of aortic rings in rats induced by acetylcholine and sodium nitroprusside(SNP) were examined respectively.The various biochemical parameters in vascular tissues or blood sera were also analyzed.Results Incubating HTL(10 mmol/L) with aortic rings for 30 min significantly inhibited EDR of isolated aortic rings,reduced nitro oxide(NO) content,increased activity of superoxide dismutase(SOD) and content of malondialdehyd(MDA) in vitro(P<0.01).The incubation of rosiglitazone(1 mmol/L) with aortic rings for 30 minutes prior to adding HTL significantly lessened HTL induced-injuries of EDR,preserved NO content,inhibited elevation of SOD activity and MDA content in aortic tissues(P<0.05 or P<0.01).Incubation of Captopril(0.03 mmol/L) and Apocynin(0.03 mmol/L) with aortic rings for 30 minutes prior to adding HTL respectively also protected the vascular endothelium from injury and the change of biochemistry parameters in aortic tissues(P<0.05 or P<0.01) in vitro.Rats were administered HTL(50 mg/(kg·d)) by gavage for 8 weeks that resulted in an inhibition of EDR of aortic rings,increases of MDA content,reduction of both paraoxonase-1(PON1) activity and NO content(P<0.01),but had no effect on activity of total nitric oxide synthase(TNOS),activity of endothelial nitric oxide synthase(eNOS),activity of induced nitric oxide synthase(iNOS) in sera and activity of erythrocytic SOD(P>0.05).The treatment of rosiglitazone(10,20 or 40 mg/(kg·d)) by gavage prior to gavage of HTL dose-dependently improved EDR of aortic rings injured by HTL in vivo,inhibited elevation of MDA content,recovered PON1 activity and NO content in sera induced by HTL(P<0.05 or P<0.01).The treatment of capropril(20 mg/(kg·d)) and apocynin(200 mg/(kg·d)) also significantly reduced injury of EDR and the changes of biochemistry parameters in sera(P<0.05 or P<0.01).The treatment of HTL in both vivo and vitro had no effect on the non-endothelium-dependent relaxation by SNP(P>0.05).Conclusion HTL-induced vascular endothelial dysfunction may relate to oxidative stress and involve in inhibiting the activation of PPARγ or down-regulating the expression of PPARγ.

Abstract:Aim To investigate mechanism for accelerated atherosclerosis in diabetic patients, effect of advanced glycosylation end-product (AGE) on the expression of peroxisome proliferator-activated receptor-γ (PPAR γ) mRNA was observed in cultured human vascular endothelial cells (ECV304). Methods The ECV304 cells were exposed to AGE-modified bovine serum albumin (AGE-BSA) of 200 mg/L (glycated with glucose of 0, 20, 50, 80 mmol/L) for 24 h, or incubated with AGE-BSA (50 mmol/L, 200 mg/L) for 0, 12, 24, 36, 48, 72 h, and were treated by AGE-BSA (50, 100, 200, 400 mg/L) for 24 h. Expression of PPARγ mRNA in ECV304 cells was measured by RT-PCR with β-actin as internal standard. Results The expressions of PPARγ mRNA were decreased by AGE-BSA incubated with glucose concentration of 20, 50, 80 mmol/L (p<0.001) and depressed by AGE-BSA (50, 100, 200, 400 mg/L), respectively. After intervention of AGE-BSA for periods of 12, 24, 36, 48, 72 h, PPARγ mRNA expression was decreased markedly (p<0.001). Conclusion AGE-BSA could decrease the expression of PPARγ mRNA in cultured human vascular endothelial cells, which might be partly involved in atherogenesis in diabetic patients.