脂肝方对NASH肝细胞自噬、线粒体及其能量代谢的影响  

Effect of Zhi-gan Decoction on Autophagy,Mitochondria and Energy Metabolism of NASH Hepatocytes

作　　者：张渐轩 陈雁[1] 李柳梅 张耀中[1] 罗莉川 胡鹏言 李蓓蕾[1] 谢博文[1] 秦楚峰 纪云西[3] 

机构地区：[1]广西中医药大学,广西南宁530001 [2]贵港市中医院,广西贵港537100 [3]浙江中医药大学附属第一医院,浙江杭州310001

出　　处：《广西中医药大学学报》2017年第2期1-4,共4页Journal of Guangxi University Of Chinese Medicine

基　　金：国家自然科学基金项目(编号:81260531;81460715);广西高等学校重点资助科研项目(编号:201102ZD023)

摘　　要：[目的]探讨脂肝方对NASH肝细胞自噬、线粒体及其能量代谢的影响。[方法]将160只SD大鼠随机分为8组:8 w正常组、8 w模型组、12 w正常对照组、12 w模型对照组、西药对照组、脂肝方低剂量组、脂肝方中剂量组、脂肝方高剂量组,8 w正常组及8 w模型组在8 w末处死,其余组大鼠均于12 w末处死。正常组及模型组予生理盐水,给药组给药4周后取血用HLPC检测血清AMP/ATP比值,ELISA法检测血清AMPK含量,取肝脏组织用透射电镜观察各组大鼠肝细胞自噬及线粒体微结构改变。[结果]与12 w模型对照组比较,西药对照组、脂肝方高剂量组、脂肝方中剂量组的AMP/ATP比值降低(P<0.05),而AMPK含量升高(P<0.05);用药组中,脂肝方高剂量组的AMP/ATP比值最低(P<0.05),AMPK含量最高(P<0.05)。透射电镜观察发现12 w模型对照组大鼠肝细胞线粒体肿胀、空泡样变较8 w模型组严重,线粒体自噬体较8 w模型组增多;而用药组肝细胞线粒体结构受损程度较12 w模型对照组明显改善,且自噬体较12 w模型对照组减少,以脂肝方高剂量组改善最为明显。[结论]脂肝方能改善肝细胞能量代谢,防止线粒体损伤,激活AMPK,可能促进了线粒体自噬降解的快速完成,以减缓或阻止肝细胞炎症坏死的发生和加重,脂肝方对NASH有一定的防治作用。[Objective] To investigate the effect of Zhi-gan decoction on autophagy, mitochondria and energy metabolism of NASH hepatocytes. [Methods] 160 SD rats were randomly divided into 8 groups： normal group of 8 weeks, model group of 8 weeks, normal control group of 12 weeks, model control group of 12 weeks, western medicine control group, Zhi-gan decoction groups of low dosage, medium dosage and high dosage. Normal group and model group of 8 weeks was sacrificed at the end of the 8th week. The rats in the other groups were sacrificed at the end of 12 weeks. Normal group and model group were given normal saline. The serum AMP/ATP ratio was measured by HLPC after 4 weeks of administration, and the AMPK content in the serum was measured by ELISA. The changes of autophagy and mitochondrial microstrueture of hepatocytes in the selected liver tissue were observed by transmission electron microscopy. [ Results ] The AMP/ATP ratio and AMPK content in the western medicine control group and Zhi-gan decoction group of high dosage decreased and increased significantly compared with that of model control group of 12 weeks （P 〈0.05）. The AMP/ATP ratio was the lowest and the AMPK content was the highest in Zhi-gan decoction group of high dosage among treatment groups. Transmission electron microscopy showed that the mitochondrial swelling of the hepatocytes and vacuolar change in the model control group of 12 weeks was significantly higher than that in the 8 w model group （P 〈0.05 ）, and the mitochondrial autophagus was more than that of the 8 w model group. The degree of mitochondrial damage of the hepatocytes in the treatment groups was significantly improved compared with that in the model control group of 12 weeks, and the autophagus was less effective than the 12 w model control group. The most significant improvement was found in Zhi-gan decoction group of high dose. [ Conclusion ] Zhi-gan decoction can improve liver cell energy metabolism, and prevent mitochondrial damage, and activate AMPK. It may contribute to

关 键 词：脂肝方 非酒精性脂肪性肝炎 自噬 线粒体微结构 

分 类 号：R285.5[医药卫生—中药学]