肝宝胶囊对非酒精性脂肪性肝病大鼠的治疗效应及对腺苷酸活化蛋白激酶通路的影响

Effect of GanBao Capsule on AMPK Pathway Activation in Rats with Nonalcoholic Fatty Liver Disease

目的探讨肝宝胶囊对非酒精性脂肪性肝病(NAFLD)大鼠的治疗效应及对腺苷酸活化蛋白激酶信号通路的影响。方法40只SD雄性大鼠随机分为4组(n=10):正常组、模型组、药物治疗组(肝宝胶囊低剂量组、肝宝胶囊高剂量组)。正常组以普通饲料喂养,其余3组经高脂饲料喂养建立NAFLD模型,药物治疗组分别予0.54 g/(kg·d)、2.16 g/(kg·d)肝宝胶囊灌胃治疗4周,模型组以蒸馏水灌胃;HE染色评估病理学改变,检测各组血清TC、TG、ALT、AST及肝组织TC、TG含量;ELISA法检测肝组织IL-6、IL^(-1)0、FFA、TNF-α含量;Real-time PCR检测肝组织AMPK、SREBP-1c mRNA表达;结果与模型组比较,药物治疗组均降低大鼠血清TC、TG、ALT、AST水平,降低肝组织FFA、TNF-α、IL-6表达,降低肝脏NAS积分;药物治疗组均升高肝组织IL^(-1)0、AMPK mRNA水平,降低SREBP-1c mRNA水平,高剂量组作用均更显著(P<0.05)。结论肝宝胶囊可能通过激活AMPK通路并抑制SREBP-1c表达改善肝脏脂质代谢及减轻肝细胞炎症治疗NAFLD。

OBJECTIVE To investigate the effect and the underlying mechanism of GanBao capsule on AMPK signal pathway in rats with nonalcoholic fatty liver disease.METHODS 40 male Sprague-Dawley(SD)rats were randomly divided into four groups:normal group,NAFLD model group,low dose group(0.54 g/(kg·d))and high dose group(2.16 g/(kg·d))of GanBao capsule.In addition to the normal group,the other three groups were fed high fat foods to induce NAFLD model.The drug intervention was administered via oral-gastric irrigation once daily for 6 times per week over a 6-week period.The rats were sacrificed at the end of 4 weeks for serum and liver tissue collection.Liver pathology was detected by using HE staining.The content of serum triglyceride(TG),total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and the levels of TC and TG in the hepatic tissue were tested by automatic biochemistry analyzer.The content of serum tumor necrosis factor(TNF)-α,free fatty acid(FFA),interleukin(IL)-6,IL^(-1)0,was surveyed and evaluated by the ELISA method.The expression of AMPK and SREBP-1c in the liver tissue was surveyed with Real Time-PCR.RESULTS Compared with the model group,the extent of pathological changes in hepatic tissues ameliorated after drug intervention according to HE staining,which the effect of high-dose group is more obvious(P<0.05).For the levels of FFA,TNF-α,IL-6,IL^(-1)0 in liver tissue,high dose group significantly decreased the levels of TNF-αand IL-6,While significantly increased IL^(-1)0(P<0.05).According to Real Time-PCR,the mRNA expression of AMPK increased significantly and SREBP-1c attenuated effectively in high-dose group(P<0.05).CONCLUSION GanBao capsule alleviates hyperlipidemia and inflammation in rats fed with high-fat diet possibly by activating AMPK pathway and suppress SREBP-1c activity to arrest the progression of nonalcoholic fatty liver disease.