复方贞术调脂胶囊对非酒精性脂肪肝LXR-α和SREBP-1c表达的影响

Effect of compound Zhenzhu Tiaozhi capsule on LXR-α and SREBP-1c expression in nonalcoholic fatty liver disease

目的观察复方贞术调脂胶囊(CZC)对非酒精性脂肪肝(NAFLD)大鼠的肝脂肪变性及调控因子LXR-α和SREBP-1c的影响。方法 60只大鼠随机分为正常组、模型组、阳性对照药辛伐他汀组(4 mg/kg)、CZC低、中、高剂量组(1.5、3、6 g/kg);采用高脂乳剂灌胃复制大鼠NAFLD模型,同时分组给药8周;取血检测血糖、胰岛素并计算胰岛素抵抗指数,观察肝脏形态学变化以及LXR-α、SREBP-1c的mRNA表达。结果 NAFLD模型大鼠出现明显肝脂肪病变,兼有胰岛素抵抗特征。与模型组比较,CZC能明显防治肝脂肪变性,显著降低NAFLD大鼠空腹血糖、胰岛素、胰岛素抵抗指数(P<0.05或P<0.01);CZC能显著下调大鼠肝组织中LXR-α和SREBP-1c mRNA的表达(P<0.05或P<0.01)。结论CZC对实验性NAFLD具有明显的防治作用,其机制可能与其调控肝组织LXR-α和SREBP-1c基因以及改善胰岛素抵抗有关。

Objective To study the effect of compound Zhenzhu Tiaozhi capsule（ CZC） on hepatic steatosis and LXR-α,SREBP-1c expression in nonalcoholic fatty liver disease（ NAFLD） in rats. Methods 60 SD rats were randomly divided into six groups, including the normal group, the model group, the positive control drug simvastatin group（4 mg/kg）,and three different doses（1.5,3 and 6 g/kg） of CZC groups. Rats were administered high-fat emulsion in order to replicate NAFLD model for 8 weeks. Blood samples were collected for determination of fasting blood glucose （ FBS ） , fasting insulin （ FINS ） and insulin resistance index（ HOMA-IR） . Liver morphological changes and LXR-α,SREBP-1c mRNA expression were detected. Results Rats model with NAFLD had obvious hepatic steatosis and insulin resistance features. Compared with the model group,CZC could significantly reduced the levels of FBS,FINS and HOMA-IR in NAFLD rats（ P〈0.05 or P〈0.01） . CZC also significantly reduced the expression of LXR-αand SREBP-1c mRNAs in liver（ P〈0.05 or P〈0.01） . Conclusion CZC distinctly prevent and treat experimental NAFLD in rats,in which the mechanism may be related with regulation of liver LXR-αand SREBP-1c mRNA expression and improvement of insulin resistance.