干预脂毒性改善糖尿病大鼠胰岛素分泌及氧化应激的损害

目的探讨干预脂毒性改善糖尿病大鼠胰岛分泌功能及氧化应激损害的机制。方法将大鼠分为4组①正常组（NC）,全程普通饲料喂养;②高脂组（HF）,全程高脂饲料喂养。糖尿病组,高脂饲料喂养8周后腹腔注射低剂量STZ（30mg/kg）,48h后行OGTT试验判断成模情况后分组。③糖尿病对照组（DM）,不给予药物干预;④血脂干预组（SIM）,灌胃辛伐他汀5mg/（kg.d）4周干预脂毒性。通过免疫组化染色观察胰岛B、A细胞形态学特点,RT-PCR测定胰腺内胰岛素原mRNA表达水平,DHE荧光染色检测胰岛中活性氧化产物ROS水平。结果与糖尿病对照组相比,干预脂毒性4周后血清胆固醇（TC）和甘油三酯（TG）水平分别下降了22.9%（P〈0.01）和57.0%（P〈0.05）。OGTT血糖水平均显著下降（P〈0.01）。胰岛中B细胞相对量是对照组的2.6倍（P〈0.01）,B细胞胞质内胰岛素水平增加了26.5%（P〈0.05）,胰岛素原mRNA表达升高18.3%（P〈0.01）;A细胞相对量减少了50%（P〈0.01）。血清丙二醛（MDA）水平和胰腺中ROS表达显著下降。结论辛伐他汀干预脂毒性4周可以显著改善糖尿病大鼠胰岛分泌功能和氧化应激损害。

Beneficial Effect of Simvastatin on Pancreatic Islet Insulin Secretion and ROS Damage in Diabetic Rats

Objective To observe the effects of Simvastatin treatment on improvement of pancreatic insulin secretion and ROS damage in diabetic rats.Methods Thirty-six male Sprague Dawley（SD）rats,aged 4-week-old,were randomly divided into four groups：（1）Normal control group（NC,n = 9）,fed with a standard chow.（2）High-fat group（HF,n = 9）,fed with extra high-fat chow.Diabetes mellitus was induced by high-fat chow feeding for 8 weeks followed by 30 mg/kg streptozoticin injection,and determined by OGTT assay.（3）DM control group（DM,n = 9）,untreated group.（4）Simvastatin group（SIM,n = 9）,treated with oral administration of simvastatin（5mg kg^-1 d^-1）for 4 weeks.OGTT was repeated at 2 weeks and 4 weeks after treatment.Morphological changes of pancreatic islet B-,A-cells were evaluated by immunohistochemistry.Insulin mRNA level was detected by RT-PCR.ROS expression in islets was assessed by immunofluorescence staining.Results Compared with DM group,OGTT values improved significantly（P〈0.01）at 4 weeks after simvastatin administration.Moreover,B-cell mass in islets was 2.6 times as that in DM group and insulin contents in B cells increased by 26.5% more（P〈0.05）.The A-cell mass in islets was decreased by 50%（P〈0.01）.The level of proinsulin mRNA expression was increased by 18.3%（P〈0.01）.Serum MDA level and ROS expression in islets decreased obviously.Serum levels of total cholesterol（TC）and triglyceride（TG）decreased significantly by 22.9%（P〈0.01）and 57.0%（P〈0.05）,respectively.Conclusion Four-week simvastatin treatment improves pancreatic insulin secretion and ameliorates ROS damages in diabetic rats.