GW4064对果糖诱导非酒精性脂肪肝小鼠的保护作用研究

Protective Effect of GW4064 on Non-alcoholic Fatty Liver Induced by Fructose in Mice

目的:研究GW4064对果糖诱导非酒精性脂肪肝(NAFLD)小鼠的保护作用。方法:小鼠随机分为正常对照组、模型组和治疗组,采用30%果糖水造模,8周后,治疗组灌胃给予GW4064(30 mg·kg^(-1)),2周后测定各组小鼠血清中葡萄糖、胰岛素、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、三酰甘油(TG)和胆固醇(CHO)水平;观察肝脏病理改变。结果:与NAFLD模型组相比,GW4064组小鼠空腹血糖及胰岛素含量降低,血清中TG、CHO和LDL-C含量显著降低,HDL-C水平显著升高。病理结果显示,GW4064能显著降低NAFLD小鼠肝脏脂肪变性,明显减轻肝脏损伤程度。结论:采用30%果糖可以成功诱导NAFLD模型,GW4064通过降低脂质沉积和增加胰岛素敏感性来改善NAFLD。

Objective： To investigate the protective effect of GW4064 on the non-alcoholic fatty liver （NAFLD） induced by fructose in mice. Methods： The mice were randomly divided into the normal control group, the model control group and GW4064 group. The model was established by feeding 30% fructose for 8 weeks, and then given GW4064 （30 mg · kg-1 ） for two weeks. The levels of fasting serum glucose, fasting insulin, triglyceride （TG）, cholesterol （CHO）, low density lipoprotein cholesterol （LDL-C） and high density lipoprotein cholesterol （HDL-C） were detected. Liver histopathological changes were observed by oil red O staining and hema- toxylin eosin （HE） staining. Results： Compared with those in the model group, the levels of fasting serum glucose, fasting insulin, TG, CHO and LDL-C were significantly decreased, and the content of HDL-C was increased after GW4064 treatment （P 〈 0.05）. The histopathologieal examination showed that the degree of liver steatosis was improved, and the liver injury was alleviated significantly in GW4064 group. Conclusion： The NAFLD model is successfully established by 30% fructose. GW4064 can exhibit the protective effect on the NAFLD in mice. The possible mechanism is associated with the improvement of insulin resistance and the decrease of blood and liver lipids.