摘要
目的:基于SIRT1/AMPK信号通路探讨茵陈蒿汤对大鼠酒精性肝病(Alcoholic liver disease,ALD)的治疗效应及分子机制。方法:将SD大鼠随机分为正常对照组、模型对照组、美他多辛50 mg/kg组、茵陈蒿汤1.75、3.50 g/kg组,采用梯度灌服不同浓度白酒制备大鼠急性酒精性肝损伤模型,造模同时灌胃相应药物或蒸馏水,连续10 d。观察大鼠整体状态,记录各组大鼠酒后行为学表现并评分;HE染色观察肝脏组织病理改变并评分;ELISA法检测大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、超氧化物歧化酶(SOD)、丙二醛(MDA)、三酰甘油(TG)、总胆固醇(TC)含量;免疫组化法检测肝组织SIRT1、p-AMPK蛋白表达。结果:与正常对照组比较,模型对照组大鼠肝脏组织中央静脉附近肝细胞出现明显病理损伤,血清ALT、AST、MDA、TC、TG含量明显升高(P<0.05或P<0.01),SOD活力显著降低(P<0.01),肝组织SIRT1、p-AMPK蛋白表达显著下调(P<0.01)。与模型对照组相比,茵陈蒿汤1.75、3.50 g/kg组大鼠肝细胞病理损伤均明显减轻,血清ALT、AST、MDA、TC、TG含量均明显降低(P<0.05或P<0.01),SOD活力显著升高(P<0.01),肝组织SIRT1、p-AMPK蛋白表达显著上调(P<0.01)。结论:茵陈蒿汤能有效减轻酒精性肝病大鼠肝脏组织损伤,其机制可能与调控SIRT1/AMPK信号通路,减轻肝细胞氧化应激和脂质蓄积相关。
Objective:To investigate the effect and molecular mechanism of Yinchenhao Decoction(YCHD)on alcoholic liver disease(ALD)based on the SIRT1/AMPK signaling pathway in rats.Methods:SD rats were randomly divided into a normal group,a model group,a metadoxine group(50 mg/kg,positive drug),and low-and high-dose YCHD groups(1.75 and 3.50 g/kg).The acute alcoholic liver injury model was induced by gradient administration of white wine of different concentrations in rats.Meanwhile,corresponding drugs or distilled water were given by intragastric administration for 10 consecutive days.The general state of rats was observed,and the behaviors of rats after white wine administration were recorded and scored.The pathological changes of liver tissues were observed and scored by HE staining.The serum content of alanine aminotransferase(ALT),aspartate aminotransferase(AST),superoxide dismutase(SOD),malondialdehyde(MDA),triglyceride(TG),and total cholesterol(TC)was detected by ELISA.The protein expression of SIRT1 and p-AMPK in liver tissues was detected by immunohistochemistry.Results:Compared with the normal group,the model group showed obvious pathological damage in liver cells near the central vein,increased serum levels of ALT,AST,MDA,TC,and TG(P<0.05 or P<0.01),blunted SOD activity(P<0.01),and down-regulated protein expression of SIRT1 and p-AMPK in liver tissues(P<0.01).Compared with the model group,the YCHD groups showed relieved pathological damage of liver cells,decreased content of ALT,AST,MDA,TC,and TG(P<0.05 or P<0.01),potentiated SOD activity(P<0.01),and up regulated protein expression of SIRT1 and p-AMPK in liver tissues(P<0.01).Conclusion:YCHD can effectively relieve liver tissue damage in rats with ALD,and its mechanism may be related to the regulation of the SIRT1/AMPK signaling pathway and reduction of oxidative stress and lipid accumulation in liver cells.
作者
杨焘
宋厚盼
陈哲
刘恒铭
李佳妮
冯瑶
仇婧玥
陈小娟
陈新怡
李亮
Yang Tao;Song Houpan;Chen Zhe;Liu Hengming;Li Jiani;Feng Yao;Qiu Jingyue;Chen Xiaojuan;Chen Xinyi;Li Liang(Hunan Provincial Key Laboratory of TCM Diagnostics,Hunan University of Chinese Medicine,Changsha 410208;Medical College,Hunan University of Chinese Medicine,Changsha 410208;College of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2022年第1期36-40,共5页
Pharmacology and Clinics of Chinese Materia Medica
基金
国家自然科学基金项目(编号:81703920)
湖湘青年科技创新人才项目(编号:2021RC3101)
湖南省大学生研究性学习和创新性实验计划项目(编号:S202010541040)
湖南中医药大学校级科研基金项目(编号:2020XJJJ012)
关键词
酒精性肝病
茵陈蒿汤
肝功能
氧化平衡
脂质蓄积
分子机制
alcoholic liver disease
Yinchenhao-Decoction
liver function
oxidative balance
lipid accumulation
molecular mechanism
作者简介
通信作者:宋厚盼,博士,副教授,从事中西医结合防治消化系统疾病和眼底病研究,E-mail:hpsong2015@126.com;杨焘,临床医学专业学生,从事中西医结合防治消化系统疾病研究,E-mail:yangtao1874@qq.com。
