高胆固醇血症对兔胰岛β细胞的影响及阿托伐他汀的干预作用
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The Influence of Hypercholesterolemia to Rabbit Islet β Cell and Intervention Effect of Atorvastatin
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    目的 研究高胆固醇血症对兔胰岛β细胞的影响及阿托伐他汀的干预作用。方法 24只新西兰白兔随机分为正常对照组、高胆固醇组及阿托伐他汀组。饲喂6周后,测空腹血脂、血糖、胰岛素浓度;行口服葡萄糖耐量试验(OGTT);取胰腺组织用免疫组织化学法观察胰岛形态;实时荧光定量PCR检测胰腺胰岛素原mRNA的表达;分光光度法测定丙二醛(MDA)、还原型谷胱甘肽(GSH)含量。结果 高胆固醇组糖负荷后30、60 min 血糖值、葡萄糖曲线下面积及胰岛素抵抗指数(HOMA-IR)升高,胰岛素敏感指数(ISI)、β细胞功能指数(HBCI/IR)降低;β细胞增生肥大,胰岛素阳性表达明显增多;胰岛素原mRNA表达上调;MDA吸光度值明显增高,GSH则降低。与高胆固醇组比较,阿托伐他汀组β细胞增生有所改善;MDA吸光度值降低,GSH则升高;胰岛素原mRNA表达、OGTT、HOMA-IR、HBCI/IR、ISI无显著差异。结论 高胆固醇通过诱导胰腺氧化-抗氧化失衡导致胰岛β细胞形态与功能受损,阿托伐他汀减轻了胰岛细胞的氧化应激,但并未改善高胆固醇诱发的糖代谢紊乱。

    Abstract:

    Aim To explore the influence of high-cholesterol to islet beta cell and intervention effect of atorvastatin. Methods Twenty-four New Zealand white rabbits were randomly divided into control group, cholesterol group and atorvastatin group, with eight rabbits in each group. After feeding for six weeks, the empty stomach blood were collected for inspected fasting blood- glucose (FBG), insulin (FINS), total cholesterol (TC), low density lipoprotein cholesterol (LDLC) and triglyceride(TG) The oral glucose tolerance test (OGTT) were examined The pancreatic tissue was taken to observe islet morphology and insulin positive cells by immunohistochemical method,to detect proinsulin mRNA expression by RT-PCR, to measure oxidative stress index: malondialdehyde (MDA) and reducing glutathione (GSH) by spectrophotometry. Results In cholesterol group after sugar load of 30 and 60 min, the blood glucose, the date of aera-under-curve(AUC) and the insulin resistance index (HOMA-IR) was increased (P<0.05), and insulin sensitive index (ISI), beta cell function index (HBCI/IR) was lower than control group (P<0.05) A great deal of beta cell hypertrophy and arrangement disorder were observed in the cholesterol group,in addition,insulin positive expression was increased The proinsulin mRNA was over-active(P<0.05) MDA absorbance value was higher than that of the control group (P<0.05), and GSH absorbance value was just the opposite (P<0.05). In atorvastatin group insulin positive expression decreased compared with high cholesterol group, MDA absorbance value was lower (P<0.05), and GSH absorbance value was just the reverse (P<0.05). Then, fasting gloucose, blood glucose after sugar load of 120 min, HOMA-IR, HBCI/IR, ISI and proinsulin mRNA express had no significant difference. Conclusions Hypercholesterolemia may induce pancreas oxidation-antioxidation system imbalance, finally lead to islet beta cell morphology and function damage. Atorvastatin can significantly reduce pancreatic tissue oxidative stress, but can not improve the sugar metabolic disorders induced by high cholesterol.

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高 婷,鹿育萨,董泽波,龚飞宇,曲润波.高胆固醇血症对兔胰岛β细胞的影响及阿托伐他汀的干预作用[J].中国动脉硬化杂志,2013,21(04):315~319.

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  • 收稿日期:2012-10-15
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