栀子苷改善大鼠非酒精性脂肪性肝病游离脂肪酸代谢的机制研究

Mechanism of geniposide in improving free fatty acid metabolism in rats with non-alcoholic fatty liver disease

观察栀子苷改善非酒精性脂肪性肝病的效果,从游离脂肪酸探讨栀子苷调节非酒精性脂肪性肝病的作用机制。健康雄性Wistar大鼠40只,随机分为4组:正常组、模型组、栀子苷组和血脂康组,每组大鼠10只,正常组大鼠给予正常大鼠饲料喂养,其余3组大鼠均采用高脂饲料喂养以诱导非酒精性脂肪性肝病,造模时间为8周,从第5周起至第8周末,栀子苷组和血脂康组分别灌服相应的药物。记录大鼠体重、肝湿重、脂肪质量;用相应方法检测肝组织TG,FFA,FAS,AMPK,ACCase及Malonyl-Co A含量,血清CHO,LDL-C的含量,血清AST,ALT的活性;观察肝脏组织肉眼及病理变化(HE染色法)。结果显示,与正常组相比,模型组大鼠的体重;肝湿重;脂肪重;血清CHO,LDL-C,ALT,AST;肝组织TG,FFA,FAS,ACCase及Malonyl-Co A含量皆显著升高(P<0.01);肝组织AMPK活性显著降低(P<0.01),肝组织肉眼外观及病理切片脂肪变性明显,并出现炎症损伤;与模型组相比,栀子苷组大鼠体重、脂肪质量、肝组织FFA含量、血清ALT,AST活性均显著降低(P<0.01),肝湿重,肝组织TG,FAS,ACCase及Malonyl-Co A含量明显降低(P<0.05),肝组织AMPK活性明显增多(P<0.05),肝脏肉眼外观及病理学表现均有所改善;与模型组相比,血脂康组大鼠的肝湿重、脂肪质量、肝组织TG,FFA和血清LDL-C水平明显降低(P<0.05);与血脂康组相比,栀子苷组大鼠的体重、脂肪质量、肝组织FFA含量均显著降低(P<0.01),其他方面无明显差异。结果表明,栀子苷具有显著的改善高脂饮食诱导的大鼠非酒精性脂肪性肝病的药理效应;其改善大鼠非酒精性脂肪性肝病的游离脂肪酸代谢是通过调节"AMPK-ACCase-Malonyl-Co A-FFA"轴来实现的。

To observe the effect of geniposide on non-alcoholic fatty liver disease（ NAFLD）,and discuss the mechanism of geniposide for NAFLD from the aspect of free fatty acid,forty healthy Wistar male rats were randomly divided into normal group,model group,geniposide and Xuezhikang group. The rats in normal group were fed with normal diets,and the rats in other 3 groups were given with high-fat diet for 8 weeks to induce the NAFLD models. From the week 5 to end of week 8,the rats in geniposide and Xuezhikang group were intervened with corresponding medicines. The body weight,liver wet weight,and fat weight of the rats were recorded.Visual and pathological changes in hepatic tissues were observed with HE staining. The contents of TG,FFA,FAS,AMPK,ACCase and Malonyl-Co A in hepatic tissue,contents of CHO and LDL-C in serum and activities of AST and ALT in serum were detected by using corresponding methods. The results showed that the body weight,liver wet weight,and fat weight of the rats,CHO,LDL-C,ALT and AST levels in serum,TG,FFA,FAS,ACCase and Malonyl-Co A levels in hepatic tissues of the rats in model group were significantly higher than those in normal group（ p〈0. 01）,while AMPK activity was significantly lower than that of the normal group（ p〈0. 01）,with obvious visual and pathological steatosis in hepatic tissues,and inflammatory injury occurred in model group. Compared with the model group,body weight of the rat,fat weight,levels of FFA in hepatic tissues,ALT and AST activities in serum,liver wet weight,TG,FAS,ACCase and Malonyl-Co A levels were significantly decreased in geniposide group（ p〈0. 01）,while the AMPK activity in hepatic tissues was significantly increased（ p〈0. 05）,with improvement in visual and pathological performance.Compared with the model group,liver wet weight,fat weight,TG and FFA levels in hepatic tissues,and LDL-C level in serum were significantly decreased in Xuezhikang group（ p〈0. 05）. Compared with Xuezhikang group,the body weight of rat,fat weight and FFA level in hepatic tissues were significantly lower in geniposide group（ p〈0. 01）,but with no significant difference in other aspects. These findings indicated that geniposide was highly effective in improving the pharmacological effect of NAFLD induced by highfat diet,and the mechanism was achieved through AMPK-ACCase-Malonyl-Co A-FFA axis.