Oxidative Stress in 5/6 Nephrectomized Rat Model: Effect of Alpha-Lipoic Acid
Oxidative Stress in 5/6 Nephrectomized Rat Model: Effect of Alpha-Lipoic Acid
复制标题
5/6 肾切除大鼠模型中的氧化应激：α-硫辛酸的作用
DOI：
10.3109/0886022x.2012.691012
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发表时间：
2012-01-01
期刊：
影响因子：
3
通讯作者：
Ding, Xiaoqiang
中科院分区：
文献类型：
--
作者：
Yu, Xiaofang;Liu, Hong;Ding, Xiaoqiang
α-硫辛酸（ALA）是一种强有力的抗氧化剂，其在改善糖尿病并发症方面的作用已被广泛报道。本研究的目的是探讨ALA在残肾（RK）疾病进展中的作用。在补充ALA（100 mg/kg体重，i. p.，每隔一天）或载体12周。RK大鼠显示SBp、肾脏MDA浓度、p65 NF-κB活性和巨噬细胞浸润增加，在第4周和第8周显著，在第12周降低。RK大鼠还表现出贫血、微量白蛋白尿、肾功能以及肾脏GSH和Vit E浓度降低。与RK媒介物组相比，这些变化在ALA处理8周时全部减弱。但8周后继续ALA治疗逆转了对SBp、肾脏MDA浓度、p65 NF-κB活性、巨噬细胞浸润、贫血、微量白蛋白尿和肾功能的有益作用，而如果在8周后停止治疗，则有益作用得以维持。此外，ALA增加蛋白尿和肾脏MDA浓度在假手术动物。总之，ALA给药可减轻氧化应激、炎症和高血压，并延缓氧化应激增强的RK大鼠肾功能的恶化，而在健康动物或氧化还原状态平衡良好的RK大鼠中，ALA可能充当促氧化剂，导致肾功能障碍。
Alpha-lipoic acid (ALA) is a powerful antioxidant, and its effect in ameliorating complications of diabetes mellitus has been widely documented. The aim of this study was to investigate the role of ALA in the disease progression of remnant kidneys (RK). Systolic blood pressure (SBp), hemoglobin, renal function, kidney malondialdehyde (MDA), glutathione (GSH), vitamin E (Vit E) concentrations, p65 nuclear factor (NF)-κB activity, and macrophage infiltration were analyzed in sham and RK rats supplemented with ALA (100 mg/kg body weight, i.p., every other day) or vehicle for 12 weeks. RK rats exhibited increases in SBp, kidney MDA concentration, p65 NF-κB activity, and macrophage infiltration, which were prominent in weeks 4 and 8 and decreased at week 12. RK rats also showed anemia, microalbuminuria, and decreased renal function and kidney GSH and Vit E concentrations. These changes were all attenuated by 8 weeks of ALA treatment compared to RK vehicle group. But the continued ALA treatment after week 8 reversed the beneficial effect on SBp, kidney MDA concentration, p65 NF-κB activity, macrophage infiltration, anemia, microalbuminuria, and renal function, while the beneficial effect was maintained if the treatment was discontinued after week 8. Furthermore, ALA increased albuminuria and kidney MDA concentration in sham animals. In conclusion, ALA administration attenuates oxidative stress, inflammation, and hypertension and delayed the deterioration of kidney function in RK rats with enhanced oxidative stress, while in healthy animals or RK rats with a well-balanced redox state, ALA may act as a pro-oxidant, contributing to renal dysfunction.