α-硫辛酸对糖尿病大鼠肾脏的保护作用及其可能的机制

摘要

Objective To verify the protective effect of alpha lipoic acid (ALA) on the kidneys of the rats with diabetes mellitus (DM), and discuss the possible mechanism. Methods Diabetic rat models were established and divided into DM group and ALA group. Meanwhile, a normal control (NC) group was set. After 6 weeks, the rats were sacrificed to detect the relevant biochemical parameters and oxidative stress indexes, and the pathological changes of the kidneys were observed. In addition, immunohistochemical staining and Western blot were employed to detect the expressions of TGF-β1, SnoN, collagen I and collagen IV proteins in the rat renal tissues. Results Compared with the NC group, the kidney weight/body weight (KW/BW), blood glucose (BG), total cholesterol (TC), triglyceride (TG) and 24-h urine protein were remarkably increased in the DM group, all the items but BG were significantly reduced in the ALA group. Compared with the NC group, the activity of total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) and catalase (CAT) was significantly reduced whereas malondialdehyde (MDA) content was increased in the DM group. Compared with the DM group, the activity of T-AOC, T-SOD and CAT were remarkably increased, while MDA content was reduced in the ALA group. Pathological examination on the kidneys indicated that renal tissue presented fibrosis changes in the DM group, renal fibrosis was obviously alleviated in the ALA group. Compared with the NC group, the levels of TGF-β1, collagen I and collagen IV in the kidneys were increased, whereas the level of SnoN was reduced in the DM group. Compared with the DM group, the levels of TGF-1, collagen I and collagen IV in the kidneys were reduced, while the level of SnoN was increased in the ALA group. Conclusions ALA may protect the kidneys of diabetic rats from injury by oxidative stress through enhancing the antioxidant ability, increasing the levels of SnoN protein, then inhibiting TGF-β1 signaling pathway and reducing the deposition of extracellular matrix.%目的 观察α-硫辛酸(ALA)对糖尿病大鼠肾脏的保护作用,并探讨其可能的作用机制.方法 复制糖尿病大鼠模型,分为糖尿病组(DM组)、糖尿病硫辛酸组(ALA组),并设置正常对照组(NC组).实验6周后处死全部大鼠,测定相应生化指标和相关氧化应激指标;HE、Masson染色观察肾组织的形态变化;免疫组织化学和Western blot检测大鼠肾组织中核转录共抑制因子(SnoN)、转化生长因子(TGF-β1)、Collagen I、Collagen IV表达水平.结果 ①DM组大鼠肾重/体重、血糖、血总胆固醇、三酰甘油、24 h尿蛋白均高于NC组,ALA组除了血糖外以上其余指标均低于DM组.②DM组总抗氧化物酶活性(T-AOC)、总超氧化物歧化酶活性(T-SOD)、过氧化氢酶活性(CAT)低于NC组,丙二醛含量(MDA)增多;ALA组T-AOC、T-SOD、CAT活性高于DM组,MDA含量降低.③病理检查显示,DM组大鼠出现肾纤维化改变,ALA组肾纤维化病变明显改善.④免疫组织化学和Western blot结果显示:与NC组相比,DM组大鼠SnoN蛋白水平降低,TGF-β1、Collagen I和Collagen IV增高;与DM组相比,ALA组SnoN蛋白水平升高,TGF-β1、Collagen I和Collagen IV降低.结论 α-硫辛酸可以增强DM大鼠肾脏的抗氧化能力,上调SnoN蛋白的表达,从而抑制TGF-β1信号通路而减少细胞外基质沉积,对糖尿病大鼠肾脏起到保护作用.