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

[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、100mg/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25mg/kg和50mg/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75mg/kg和100mg/kg两个高剂量干预组。[结论]25mg/kg和50mg/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(75～100mg/kg)保护作用不如低剂量组。

[ Objective ] To investigate the protective effects of ct-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 100mg/kg by garage, 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 ceils 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 100mg/kg α-LA interference. [ Conclusion ] a-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.