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目的:探讨艾赛那肽对2型糖尿病(type 2 diabetes mellitus，T2DM)大鼠胰岛β细胞凋亡的保护作用及其分子机制。方法:大鼠高脂喂养后，采用链脲佐菌素(streptozotocin，STZ)30 mg/kg腹腔注射，选择血糖值>16.7 mmol/L作为T2DM大鼠模型。将造模成功大鼠分为模型组、二甲双胍组、艾赛那肽组，每组10只。模型组灌服相同体积生理盐水，二甲双胍组灌胃给药二甲双胍200 mg/kg，艾赛那肽组皮下注射艾赛那肽10 μg/kg，每天2次。6周后检测大鼠空腹血糖(fasting blood glucose，FBG)、空腹胰岛素(fasting insulin，FINS)水平和胰腺组织超氧化物歧化酶(superoxide dismutase，SOD)、丙二醛(malonaldehyde，MDA)水平；Western blot法检测胰岛素受体底物2(insulin receptor substrate 2，IRS-2)、人Bcl-2相关X蛋白(Bcl-2 associated X protein，BAX)、Cleaved caspase-3蛋白表达；原位末端脱氧核苷酸转移酶标记法(TdT-mediated dUTP nick-end labeling，TUNEL)联合免疫组化法检测胰岛β细胞凋亡率。结果:艾赛那肽组大鼠中FBG、FINS表达水平和胰岛素抵抗指数(homeostasis model assessment insulin resistance，HOMA-IR)均较模型组明显降低，差异具有统计学意义[(18.69±1.77)mmol/L比(25.71±2.39)mmol/L，(21.60±3.58)mU/L比(26.02±4.68)mU/L，(17.79±2.46)比(29.72±5.97)，n t值分别为2.219，2.699和3.584，n P值均<0.05]；艾赛那肽组MDA和SOD含量也较对照组明显降低，差异具有统计学意义[(8.48±1.37)nmol/mL比(10.65±2.00)nmol/mL，(181.69±30.46)U/mL比(124.90±41.55)U/mL，n t值分别为2.864和5.698，n P值均<0.05]。此外，艾赛那肽能够上调IRS-2蛋白表达，降低BAX、Cleaved caspase-3表达水平(n t值分别为4.535，3.232和5.297，n P值均<0.05)，并降低T2DM大鼠胰岛β细胞凋亡率(n t＝2.598，n P16.7 mmol/L after feeding with high-fat diet.The successful model rats were divided into model group, metformin group, exenatide group with 10 rats in each group.Model group were given the same volume of saline.Metformin group was given metformin 200 mg/kg and the exenatide group was injected subcutaneously with subcutaneous injection at 10 μg/kg twice a day.Six weeks later the fasting blood glucose (FBG), fasting insulin (FINS) and superoxide dismutase (SOD), malonaldehyde (MDA) in pancreatic tissue were measured.The expression of insulin receptor substrate 2(IRS-2), Bcl-2 associated X protein (BAX), Cleaved caspase-3 were detected by Western blot.The apoptosis rate of pancreatic β cells was examined by TdT-mediated dUTP nick-end labeling (TUNEL) with immunohistochemical staining.Results:The expression level of FBG, FINS and homeostasis model assessment insulin resistance(HOMA-IR) in the exenatide group were significantly lower than those in the model group [(18.69±1.77) mmol/L vs (25.71±2.39) mmol/L, (21.60±3.58) mU/L vs(26.02±4.68)mU/L, (17.79±2.46)vs(29.72±5.97), n t values were 2.219, 2.699 and 3.584, respectively, all n P values <0.05]. At the same time, the MDA and SOD contents in the exenatide-treated group were also significantly lower than those of the control group [(8.48±1.37) nmol/mL vs (10.65±2.00) nmol/mL, (181.69±30.46) U/mL vs (124.90±41.55) U/mL, n t values were 2.864 and 5.698, respectively, all n P values <0.05]. Exenatide can up-regulate the expression of IRS-2 protein, reduce the expression of BAX and Cleared caspase-3 ( n t values were 4.535, 3.232 and 5.297 respectively, all n P values <0.05), and significantly decrease the apoptosis rate of islet β cells in T2DM rats ( n t=2.598, n P<0.05).n Conclusion:Exenatide can protect the apoptosis of pancreatic β cell in T2DM rats, which might be associated with the enhancement of the ability of antioxidant and upregulation of the expression of IRS-2.