苯那普利对糖尿病大鼠胰岛细胞功能的影响

Influences of benazepril on pancreatic islet β-cell function in rats with type 2 diabetes mellitus

目的研究苯那普利对糖尿病大鼠胰岛细胞功能的影响。方法采用长期高脂饮食加小剂量链脲菌素(STZ,30mg/kg)腹腔注射建立2型糖尿病大鼠模型,以苯那普利10mg·kg-1.d-1进行干预,2个月后行口服葡萄糖耐量试验(OGTT)检测胰岛细胞功能,试剂盒检测胰腺组织丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性,HE染色和免疫组化对胰腺形态学及十二指肠同源框蛋白-1(PDX-1)进行观察。结果DM组大鼠葡萄糖刺激的胰岛素分泌明显延迟,MDA含量(7.10±0.21)nmol/mg较NC组(3.25±0.12)nmol/mg显著升高(P<0.01),SOD活性(38.9±2.1)U/mg较NC组(51.01±1.47)U/mg显著降低(P<0.01),免疫组化胰岛素染色阳性面积(12.8±2.2)%及PDX-1平均光密度0.240±0.051显著低于NC组[(42.6±2.7)%,(0.648±0.087)nmol/mg](P<0.01),苯那普利干预后胰岛素释放曲线基本接近正常形态,MDA含量(5.87±0.19)nmol/mg较DM组显著降低(P<0.01),SOD活性(45.3±1.7)较DM组显著升高(P<0.01),免疫组化胰岛素染色阳性面积(18.8±2.7)%及PDX-1平均光密度0.40±0.044较DM组显著增高(P<0.01)。结论苯那普利可以减轻糖尿病大鼠氧化应激反应,并上调PDX-1的表达,改善胰岛细胞功能。

Objective To investigate the influences and the pathogenesis of angiotensin converting enzyme inhibitor-benazepril on pancreatic islet β-cell function in the development of type 2 diabetes of rats. Methods Type 2 diabetes models of rats were induced by long-term high-fat feeding combined with intraperitoneal injection of streptozotocin （STZ30 mg/kg）,then after 2-month intervention with benazepril （10mg/kg/d）,the islet β-cell function was evaluated by oral glucose tolerance test,and MDA and SOD content in pancreatic islet were measured with kits according to the instruction. The morphological changes of pancreas in tissue specimens were examined by microscopy and immunohistochemistry. Results In rats with type 2 diabetes mellitus ,the first-phase insulin secretion was significantly delayed ,and MDA content（7.10±0.21）was significantly higher than that （3.25±0.12） in control group （P〈0.01）,and SOD content （38.89±2.07）was significantly lower than that （51.01±1.47）in control group （P〈0.01）,the percentage of insulin-positive cells（12.75±2.18） and the average optical density of PDX-1-positive areas（0.240±0.051） were significantly lower than those （42.61±2.68,0.648±0.087） in control group （P〈0.01）.The first-phase insulin secretion was significantly improved in benazepril treatment group,and MDA content（5.87±0.19） was obviously lower than that in the diabetic rats who were not treated（P〈0.01）,and SOD content（45.29±1.73） was significantly increased （P〈0.01）,the percentage of insulin-positive cells（18.78±2.67） and the average optical density of PDX-1-positive areas（0.40±0.044） were obviously increased,as compared with those of diabetic rats who were not treated （P〈0.01）. Conclusion The benazeprilcan relieve the stress reaction of diabetic rats,up-regulate the expression of PDX-1 and improve pancreatic islet β-cell function.