α-硫辛酸对2型糖尿病大鼠氧化应激致胰岛细胞凋亡的影响

Effects of Alpha-Lipoic Acid on Oxidative Stress Induced Pancreatic Islet Cell Apoptosis in Type 2 Diabetic Rats

[目的]研究α-硫辛酸对2型糖尿病大鼠氧化应激致胰岛细胞凋亡的影响。[方法]采用高热量饮食联合腹腔注射低剂量链脲菌素制备2型糖尿病大鼠模型(模型对照组),予以α-硫辛酸(15、30、60和120 mg/kg体质量)干预处理12周后,检测大鼠胰腺组织氧化应激指标和胰岛细胞凋亡情况,同时检测胰腺组织中凋亡相关蛋白的表达改变。[结果]与模型组相比,各干预组大鼠胰腺组织中丙二醛含量均明显降低(P<0.01),总超氧化物歧化酶和谷胱甘肽过氧化物酶活性则明显升高(P<0.01);除15 mg/kg体质量组外,其余各干预组大鼠胰岛凋亡指数较模型组均明显降低(P<0.01),其中以60 mg/kg体质量干预组效果最好。与模型组比较,各干预组大鼠胰腺组织中Bax、Fas、活化型Caspase-9和Caspase-3等蛋白表达均降低,而Bcl-2蛋白表达则明显增高。[结论]α-硫辛酸可通过调节大鼠胰腺组织的氧化应激状态,改变凋亡相关蛋白的表达水平,显著降低2型糖尿病模型大鼠胰岛细胞的凋亡率,增加机体胰岛素的分泌水平。

[ Objective ] To assess the effects of alpha-lipoic acid on oxidative stress induced pancreatic islet cell apoptosis in type 2 diabetic rats. [ Methods ] High-calorie diet combined with intraperitoneal injection of low-dose streptozotocin was used to establish a type 2 diabetic rat model. Then the model rats were treated by alpha-lipoic acid （15, 30, 60, and 120mg/kg body weight） for 12 weeks before detecting pancreatic oxidative stress, apoptosis of pancreatic ceils, and changes in the expression levels of pancreatic apoptosis-related proteins. [ Results ] The pancreatic malondialdehyde levels were significantly decreased in all alpha-lipoic acid intervented groups （P〈 0.01）, while the total superoxide disumutase and the glutathione peroxidase activities were significantly increased （P 〈 0.01）, compared with the model control rats. The apoptotic indices were significantly decreased （P 〈 0.01） in all intervention groups except the 15 mg/kg body weight group, compared with the model control rats, and the highest intervention effect was found in the 60 mg/kg body weight group. The protein levels of Bax, Fas, activated Caspase-9 and Caspase-3 decreased, and the Bcl-2 protein level increased significantly in all intervention groups. [Conclusion] Apoptosis rates of pancreatic cells are down-regulated by alpha-lipoic acid via ameliorating pancreatic oxidative stress and related protein levels.