基于内源性大麻素探讨皂术抗纤方治疗肝纤维化大鼠的作用机制  

Mechanism of Zaozhu Kangxian Formula in the treatment of liver fibrosis based on endogenous cannabinoid

作　　者：林立[1] 陈少东[2] 许诗霖 吴春城[1] 周志佳 赖鹏华[2] 吴耀南[1] 郑晓婷 刘垚昱 蒋晓倩 梁惠卿[1] LIN Li;CHEN Shao-dong;XU Shi-lin;WU Chun-cheng;ZHOU Zhi-jia;LAI Peng-hua;WU Yao-nan;ZHENG Xiao-ting;LIU Yao-yu;JING Xiao-qian;LIANG Hui-qing(Liver Disease Center,Xiamen Hospital of Traditional Chinese Medicine,Xiamen 361009,China;Department of Traditional Chinese Medicine,Medical College of Xiamen University,Xiamen 361102,China;Department of Traditional Chinese Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 351012,China)

机构地区：[1]厦门市中医院肝病中心,厦门361009 [2]厦门大学医学院中医系,厦门361102 [3]福建中医药大学中医系,福州351012

出　　处：《中华中医药杂志》2021年第4期1917-1920,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81873242);“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项2017年度课题(No.2017ZX10202201);福建省医学创新科研人才培养项目(No.2018-CXB-28,No.2018-2-68);厦门市重要重大疾病联合攻关项目(No.3502Z20179047);厦门市医疗卫生指导性项目(No.3502Z20209121);厦门康氏肝病学术流派传承工作室;全国第六批老中医药专家学术经验继承工作(2017年);厦门市第五批中青年中医后备人才培养项目。

摘　　要：目的:基于内源性大麻素研究皂术抗纤方对肝纤维化大鼠的药理效应及其作用机制。方法:按照随机数字表法将40只Wistar雄性大鼠随机分为正常组、模型组、皂术抗纤方组和安络化纤丸组,每组10只。模型组、皂术抗纤方组和安络化纤丸组给予四氯化碳(CCl4)腹腔注射8周,复制肝纤维化模型。第5~8周,皂术抗纤方组、安络化纤丸组分别给予皂术抗纤方(16.1g/kg)、安络化纤丸(30g/kg)治疗。检测各组大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平,肝组织羟脯氨酸(Hyp)、N-花生四烯酸氨基乙醇(AEA)、2-花生四烯酸甘油(2-AG)及内源性大麻素水解酶脂肪酰胺水解酶(FAAH)、单酰基甘油酯酶(MGL)mRNA表达量变化。结果:与正常组比较,模型组大鼠肝组织出现明显肝纤维化,血清ALT、AST水平及肝组织Hyp、AEA、2-AG含量显著升高(P<0.01),FAAH、MGL mRNA表达显著降低(P<0.01)。与模型组比较,皂术抗纤方组、安络化纤丸组血清ALT、AST水平及肝组织Hyp含量均显著降低(P<0.01),皂术抗纤方组肝组织大麻素AEA、2-AG含量显著降低(P<0.01),FAAH、MGL mRNA表达显著升高(P<0.01)。结论:皂术抗纤方治疗肝纤维化效果显著,其作用机制与调节内源性大麻素有关。Objective:To study the pharmacological effect of Zaozhu Kangxian Formula on hepatic fibrosis rats and the mechanism of action on endogenous cannabinoid.Methods:Forfy Wistar male rats were randomly divided into normal group,model group,Zaozhu Kangxian Formula treatment group and Anluo Huaxian Pill group,with 10 rats in each group.During 8 weeks,the normal group was fed with common diet,while the model group,Zaozhu Kangxian Formula treatment group and Anluo Huaxian Pill group were given intraperitoneal injection of carbon tetrachloride(CCl4)to replicate the liver fibrosis model.Starting from the 5 th week,Zaozhu Kangxian Formula treatment group was given Zaozhu Kangxian Formula(16.1 g/kg),and Anluo Huaxian Pill group was given Anluo Huaxian Pill(30 g/kg)by gavage for 4 weeks.The changes of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST),hepatic hydroxyproline(Hyp)staining,endogenous cannabinoid N-arachidonic acid aminoethanol(AEA),arachidonic acid glycerol(2-AG)content and the mRNA expressions of endogenous cannabinoid hydrolase lipase fatty amide hydrolase(FAAH)and monoglyceride esterase(MGL)in rat liver tissue were detected.Results:Compared with the normal group,liver fibrosis was observed in the model group,the levels of ALT and AST in serum,the contents of Hyp,AEA and 2-AG in liver tissue were significantly increased(P<0.01),and the mRNA expressions of FAAH and MGL were decreased(P<0.01).Compared with the model group,the serum ALT,AST,hepatic Hyp contents in the Zaozhu Kangxian Formula treatment group and Anluo Huaxian Pill group decreased significantly(P<0.05),while AEA and 2-AG in liver tissue decreased(P<0.01)and the expression of mRNA in FAAH and MGL increased in Zaozhu Kangxian Formula treatment group(P<0.01).Conclusion:Zaozhu Kangxian Formula has a good therapeutic effect on hepatic fibrosis,and its mechanism is closely related to the inhibition of endogenous cannabinoid.

关 键 词：皂术抗纤方 肝纤维化 内源性大麻素 N-花生四烯酸氨基乙醇 2-花生四烯酸甘油 脂肪酰胺水解酶 单酰基甘油酯酶 

分 类 号：R285.5[医药卫生—中药学]