非酒精性脂肪性肝病大鼠肝组织瘦素受体表达的变化

CHANGE IN THE EXPRESSION OF LEPTIN RECEPTORS IN LIVER OF RATS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

目的检测高脂饮食诱发的非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)大鼠肝组织瘦素受体的表达,探讨NAFLD瘦素抵抗的发生机制及瘦素抵抗在NAFLD发病中的作用。方法采用高脂饮食制备Wist-ar大鼠NAFLD模型;ELISA法测定大鼠血清瘦素(leptin,LP)浓度;全自动生化分析仪测血清甘油三酯(triglyceride,TG)、空腹血糖(fasting blood glucose,FBG),比色法测游离脂肪酸(free fatty acid,FFA),放射免疫法测空腹血清胰岛素(fasting insulin,FINS),计算空腹状态下胰岛素抵抗指数;对肝组织分别进行HE染色、苏丹Ⅳ染色、瘦素受体免疫组化染色,并进行半定量分析。利用SAS 8.0统计软件处理实验数据。结果模型组大鼠肝组织瘦素受体表达比正常组明显减弱,且与血清瘦素浓度、游离脂肪酸、胰岛素敏感指数、肝细胞脂变、炎症活动度显著负相关,相关系数分别为r=-0.83,-0.71,-0.65,-0.83,-0.87。多元线性回归分析显示,瘦素受体表达减弱是肝脂变的独立影响因素。结论肝组织瘦素受体表达减弱是NAFLD瘦素抵抗的重要病理机制之一,瘦素抵抗与胰岛素抵抗相互作用,共同促进了脂肪肝的发生发展。

Objective To investigate the expression of leptin receptors in liver of rats with non-alcoholic fatty liver disease （NAFLD） induced by fat-rich diet and to delineate the pathogenesis of NAFLD. Methods The male Wistar rat model of NAFLD was established by fat-rich diet. Enzyme-linked immunosorbent assay （ELISA） was used for quantitative measurement of serum leptin. The levels of triglyceride, free fatty acid, fasting blood glucose, and fasting insulin were also assayed. The histological manifestation of liver was anaryzed by means of HE staining, Sudan IV staining and immunohistochemical method. All data were processed with software SAS 8.0. The t-test was used to compare the two groups. Simple correlation and linear-regression analysis were used for correlation analysis. Results The relative quantity of leptin, receptors in steatotic liver was remarkably lower cornpared with that in normal liver. The expres,ion of.,leptin receptor in the liver of model rats was negatively correlated with serum leptin concentration （r = -0. 83）,insulin resistance index （r = -0. 65）, hepatic steatosis （r =-0. 83） and hepatic inflammation （r= -0. 87）, and it had an independent effect on hepatic steatosis. Conclusion The low expression of leptin receptor in the liver of model rats is one of the pathogenesis of leptin resistance in NAFLD.Leptin resistance and insulin resistance interact to accelerate the development of NAFLD.