2型糖尿病大鼠氧化应激介导肝脏和骨骼肌细胞内脂肪堆积的差异

目的观察2型糖尿病大鼠高脂饮食后肝脏和骨骼肌氧化应激及脂质堆积的差异。方法10只雄性Goto Kakisaki（GK）大鼠随机分为两组：糖尿病对照组和糖尿病硫辛酸治疗组（α-硫辛酸35mg／kg隔天腹腔内注射1次），健康Wistar大鼠4只为正常对照组，高脂饮食12周。测定各组大鼠肝、骨骼肌匀浆中的GSH、SOD和MDA及脂质谱水平，以及观察其组织病理形态学改变。结果糖尿病对照组肝组织GSH、SOD和MDA及脂质谱水平较正常对照组明显异常，经α-硫辛酸治疗后有明显改善，且GSH、SOD和MDA水平与甘油三酯水平相关；骨骼肌组织中除SOD外，GSH和MDA以及脂质谱水平在3组之间的变化，差异无统计学意义（P〉0．05）。糖尿病对照组有明显的肝细胞脂肪变性、坏死及炎性细胞浸润，硫辛酸治疗后有明显改善，而骨骼肌组织病理形态学无明显变化。结论12周高脂饮食可导致明显的氧化应激状态和细胞内脂肪堆积，但肝脏和骨骼肌两者之间存在一定差异，α-硫辛酸通过改善氧化应激状态而对细胞脂质代谢异常有明显的缓解作用。

Differences in accumulation of lipid in liver and skeletal muscle mediated by oxidative stress in type 2 diabetic rats

Objective To investigate the differences in oxidative stress status and accumulation of lipid between liver and skeletal muscle of type 2 diabetic rats with high-fat diet. Methods Four healthy Wistar rats （ normal control group） and 10 Goto Kakisaki （GK） rats were random divided into two groups ： diabetic control group and lipoic acid-treated diabetic group （ lipoic acid 35 mg/kg intrapefitoneal injection qd alt） , both of which were fed with high-fat diet for 12 weeks. Malonaldehyde （MD） , Aglutathione （GSH） , superoxide dismutase （SOD） , total cholesterol （TC） , triglycefide （TG） and free fatty acid （FFA） in liver and skeletal muscle homogenate were measured. Pathomorphologic changes of liver and muscle were assessed. Results There were significant differences in levels of GSH, SOD, MDA and lipid profile in liver homogenate between diabetic control group and normal control group （ P 〈0. 01 ）. The measurements of parameters in liver homogenate were improved in lipoic acid-treated diabetic group compared with diabetic control group （ P 〈 0. 05 - 0. 01 ）. There were significant correlations between the levels of GSH, SOD, MDA and TG in liver homogenate. However, except for SOD, there were no significant differences in the levels of GSH, MDA and lipid profile in muscle homogenate between groups. Compared with normal control group, there were overt steatosis and necrosis of hepatocytes, infiltration of inflammatory cells in diabetic control group which were improved by administrated with lipoic acid. However no significant morphologic changes in muscle were showed between two groups. Conclusion There were differences in oxidative stress status and intracellular accumulation of lipid induced by high-fat diet for 12 weeks between liver and muscle in type 2 diabetic rats. Anfioxidant α-lipoic acid can improve intracellular lipid levels possible by preventing the oxidative stress.