基于内源性大麻素探讨皂术茵陈方治疗非酒精性脂肪性肝炎的作用机制  

Mechanism of Zaozhu Yinchen Recipe for Treatment of Non-alcoholic Steatohepatitis Based on Endogenous Cannabinoid

作　　者：庄鸿莉[1] 张利敏[2] 许诗霖 梁惠卿[3] 赖鹏华[2] 高凉琴 许玲夏 周志佳 陈少东[2] ZHUANG Hong-li;ZHANG Li-min;XU Shi-lin;LIANG Hui-qing;LAI Peng-hua;GAO Liang-qin;XU Ling-xia;ZHOU Zhi-jia;CHEN Shao-dong(Department of Traditional Chinese Medicine,First Hospital of Xiamen University,Fujian,361001;School of Medicine,Xiamen University,Fujian,361102;Liver Disease Center,Xiamen Hospital of Traditional Chinese Medicine,Fujian,361009;Department of Traditional Chinese Medicine,of Xiamen University Hospital,Fujian,361005)

机构地区：[1]厦门大学附属第一医院中医科,福建361001 [2]厦门大学医学院,福建361102 [3]厦门市中医院肝病中心,福建361009 [4]厦门大学医院中医科,福建361005

出　　处：《中国中西医结合杂志》2019年第11期1355-1358,共4页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.81503529,No.81673660);福建省科技计划引导性项目(No.2015D0007,No.2016D012);厦门市科技计划项目(No.3502Z20174028);厦门市重要重大疾病联合攻关项目(No.3502Z20179047);福建中医药大学临床专项校管课题基金(No.XB2016080)

摘　　要：目的研究皂术茵陈方对非酒精性脂肪性肝炎大鼠的药理效应及对内源性大麻素的作用机制。方法30只Wistar雄性大鼠随机分为正常组、模型组和治疗组,每组10只。造模12周期间,正常组给予普通饲料喂养,模型组和治疗组给予高脂饲料以复制非酒精性脂肪性肝炎模型。从第7周开始,治疗组给予皂术茵陈方灌胃治疗6周。检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性,肝组织甘油三酯(TG)、总胆固醇(TC);HE染色法观察大鼠肝组织的病理变化;采用高效液相色谱-质谱联用法(LC/MS)检测肝组织2-花生四烯酸甘油(2-AG)含量;通过Real-time PCR法检测大鼠肝组织脂肪酰胺水解酶(FAAH)和单酰基甘油酯酶(MGL)mRNA表达水平。结果与正常组比较,模型组大鼠肝组织内出现明显脂肪沉积和炎症损伤,血清ALT、AST活性明显升高(P<0.01),肝组织TG、TC含量升高(P<0.01);肝组织大麻素2-AG含量显著升高(P<0.01),FAAH、MGL mRNA表达降低(P<0.01)。治疗组与模型组比较,治疗6周后血清ALT、AST活性、肝组织TG、TC、大麻素2-AG含量明显降低(P<0.05),FAAH、MGL mRNA表达升高(P<0.01)。结论皂术茵陈方对非酒精性脂肪性肝炎具有良好的治疗作用,其作用机制与抑制内源性大麻素密切相关。Objective To study the pharmacological effect of Zaozhu Yinchen Recipe(ZZYCR)on nonalcoholic steatohepatitis(NASH)rats and to observe the mechanism of action on endogenous cannabinoid.Methods Thirty Wistar male rats were randomly divided into the normal group,the model group,and the treatment group,10 in each group.During the 12 weeks of modeling,rats in the normal group were fed with common forage.NASH model was duplicated in rats of the model group and the treatment group by feeding high-fat forage.Starting from the 7 th week,ZZYCR was administered to rats in the treatment group by gastrogavage for 6 successive weeks.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),and total cholesterol(TC)were detected.Pathological changes of rat liver tissues were observed by HE staining.The content of 2-arachidonoyl glycerol(2-AG)in liver tissue was detected by LC/MS,and the mRNA expression levels of fatty amide hydrolase(FAAH)and monoglyceride esterase(MGL)in liver tissue were detected by Real-time PCR.Results Compared with the normal group,obvious fat deposition and inflammation injury occurred in the liver tissue,activities of ALT and AST in serum increased significantly(P<0.01),the contents of TG and TC in liver tissue increased significantly(P<0.01),the contents of 2-AG in liver tissue increased significantly(P<0.01),and the mRNA expressions of FAAH and MGL decreased in the model group(P<0.01).After 6 weeks of treatment,serum activities of ALT and AST,contents of TG,TC,and 2-AG in liver tissue significantly decreased(P<0.05),and the mRNA expressions of in FAAH and MGL increased(P<0.01)in the treatment group.Conclusion ZZYCR showed good therapeutic effects on NASH,and its mechanism was closely related to inhibiting endogenous cannabinoid.

关 键 词：皂术茵陈方 非酒精性脂肪性肝炎 内源性大麻素 

分 类 号：R[医药卫生]