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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

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【作者】 陶功华王莉萍俞筱琦施志冲洪新宇帅怡王宁肖萍

【Author】 TAO Gong-hua;WANG Li-ping;YU Xiao-qi;SHI Zhi-chong;HONG Xin-yu;SHUAI Yi;WANG Ning;XIAO Ping;Division of Toxicology, Shanghai Municipal Center for Disease Control and Prevention;

【机构】 上海市疾病预防控制中心毒性评价科

【摘要】 [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。

【Abstract】 [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 120 mg/kg body weight) for 12 weeks before detecting pancreatic oxidative stress, apoptosis of pancreatic cells, 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.

【基金】 上海市卫生局资助项目(编号:20114068)
  • 【文献出处】 环境与职业医学 ,Journal of Environmental & Occupational Medicine , 编辑部邮箱 ,2014年04期
  • 【分类号】R114;R587.1
  • 【被引频次】14
  • 【下载频次】224
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