罗格列酮对非酒精性脂肪性肝炎大鼠脂质过氧化的影响

Effects of rosiglitazone on lipid peroxidation in nonalcoholic steatohepatitis rats

目的探讨罗格列酮对非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)大鼠脂质过氧化的影响。方法 30只雄性SD大鼠均分为正常组、模型组和罗格列酮预防组,每组各10只。模型组和罗格列酮预防组高脂喂养12周制备NASH模型,罗格列酮预防组同时每天予4mg/kg罗格列酮灌胃。第12周末处死动物,并收集血清和肝组织,检测糖代谢、脂代谢、肝功能和脂质过氧化指标变化。结果与正常组相比,模型组空腹血糖、血清胰岛素、胰岛素抵抗指数(HOMA-IRI)升高,血清和肝匀浆脂代谢紊乱,ALT、AST和γ-谷氨酰转移酶(GGT)明显升高。与模型组相比,罗格列酮预防组糖脂代谢、ALT、AST等指标明显下降(P<0.01)。模型组血清和肝匀浆总抗氧化能力(total anti-oxidation competence,T-AOC)、超氧化物歧化酶(T-SOD)、过氧化氢酶(catalase,CAT)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)、丙二醛(malondialdehyde,MDA)较正常组变化明显,而罗格列酮预防组可显著改善上述脂质过氧化指标(P<0.05)。结论罗格列酮可全面、有效地减轻NASH大鼠脂质过氧化紊乱,改善胰岛素抵抗。

Objective To explore the effects of rosiglitazone on lipid peroxidation in nonalcoholic steatohepatitis rats.Methods Thirty Sprague-Dawley male rats were randomly assigned into normal group,model group,and rosiglitazone prevention group,with 10 rats in each.Rats in the rosiglitazone prevention group were given 4 mg·kg·d^（-1） gavage daily.After 12 weeks,the rats were sacrificed,then biochemical parameters of liver function,lipid metabolism,glycometabolism, and antioxidant enzyme activities from serum and hepatic samples were estimated by using automatic biochemical analyzer and ELISA,respectively.Results Compared with normal group,model group showed a significant increase in the serum levels of fasting blood glucose, insulin and HOMA-IRI,but a decrease（P0.01 ） in insulin sensitivity index（ISI）.It also showed disorder in serum and hepatic lipid metabolism,and an increase in TC,TG,LDL-C, and free fatty acids,but a decrease in HDL-C.The levels of serum ALT,AST and GGT in high-fat-diet-fed rats were significantly increased.The serum and hepatic levels of oxidation-reduction indicators of total anti-oxidation competence,superoxide dismutase,catalase and glutathione peroxidase decreased.Malondialdehyde was significantly progressive.Rosiglitazone intervention resulted in a remarkable improvement in all of those indicators（P0.05）. Conclusions Rosiglitazone can reduce effectively and comprehensively lipid peroxidation disorder and improve insulin resistance in NASH rats.