α-硫辛酸对高糖诱导GK大鼠肝氧化损伤的影响
Effects of α-Lipoic Acid on Liver Oxidative Damage Induced by Hyperglycemia in GK Rats
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摘要:
目的 探讨α-硫辛酸(α-LA)对高糖诱导GK 大鼠肝氧化损伤的影响。 方法 选用GK 大鼠36 只,分为6 组,阴性对照组普通饮水、阳性对照组及4 个干预组分别给予等量30%蔗糖饮水,干预组分别给予不同剂量的α-LA(25、50、75、100 mg/kg)灌胃。干预9 周后观察不同剂量的α-LA对高糖诱导下GK大鼠肝组织脂质过氧化水平、抗氧化酶活力以及肝线粒体活性氧(ROS)水平的影响。 结果 阳性对照组大鼠丙二醛(MDA)和线粒体ROS 水平明显高于阴性对照组(P<0.05),而超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)水平明显低于阴性对照组(P<0.05),提示高糖饮水明显增加了GK大鼠肝脏的氧化应激水平。在高糖诱导情况下,各α-LA干预组与对照组比较,给予25 mg/kg 和50 mg/kg 剂量的α-LA干预可以有效降低肝组织MDA浓度,提高SOD、GSH-P 活性以及降低肝线粒体ROS 水平(P<0.05),其抗氧化损伤的效果好于75 mg/kg 和100 mg/kg 两个高剂量干预组。 结论 25 mg/kg 和50 mg/kg 剂量的α-LA对高糖诱导的GK大鼠肝组织的氧化损伤具有保护作用,但这种保护作用并未呈现明显的剂量作用关系,高剂量的α-LA(75~100 mg/kg)保护作用不如低剂量组。 Abstract:Objective To investigate the protective effects of α-lipoic acid (α-LA) on sucrose-induced liver oxidative damages in Goto-Kakizaki (GK) rats. Methods Thirty-six eight-week-old male GK rats were randomly divided into 6 groups:1 negative control (no treatment), 1 positive control (30% sucrose solution), and 4 experimental (30% sucrose solution+daily α-LA supplementation of 25, 50, 75, or 100 mg/kg by gavage, respectively) groups. Nine weeks after the interference, changes in lipid peroxidation concentrations, antioxidases activity, and reactive oxygen species (ROS) levels in liver mitochondria were recorded. Results The levels of malondialdehyde (MDA) and ROS increased significantly (P< 0.05), and the activities of superoxidase dismutase (SOD) and glutathione peroxidase (GSH-Px) in mitochondria of liver decreased remarkably in the positive control rats compared with those of the negative control rats (P< 0.05), which indicated that sucrose feeding obviously enhanced oxidative stress in the liver cells of GK rats. Compared with the positive control rats, the rats treated with 25 or 50 mg/kg α-LA showed significant declines in the levels of MDA and ROS and increases in the activities of GSH-Px and SOD in mitochondria of rat liver (P< 0.05), and the above antioxidative effects were superior to the similar indicators in the rats with 75 and 100 mg/kg α-LA interference. Conclusion α-lipoic acid within a certain range of concentration may have a protective effect on the oxidative damage in liver cells of sucrose-induced GK rats.
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