2020 年第 9 期 第 15 卷

基于代谢组学研究雷公藤红素对非酒精性脂肪性肝炎小鼠的治疗作用及其机制

Therapeutic effect and mechanism of celastrol on nonalcoholic steatohepatitis mice based on metabolomics

作者：朱子家王文斌沈志博薛文华赵杰

英文作者：hu Zijia Wang Wenbin Shen Zhibo Xue Wenhua Zhao Jie 

单位：郑州大学第一附属医院药学部450052

英文单位：Department of Pharmacy First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China

关键词：非酒精性脂肪性肝炎；雷公藤红素；代谢组学；蛋氨酸-胆碱缺乏饮食

英文关键词：Nonalcoholicsteatohepatitis;Celastrol;Metabolomics;Methionine-cholinedeficiencydiet

• 摘要：

• 目的 通过代谢组学的分析手段探讨雷公藤红素（CEL）干预对蛋氨酸-胆碱缺乏（MCD）饮食诱导的非酒精性脂肪性肝炎模型小鼠的治疗作用及其机制。方法 选取24只雄性无特定病原体级C57BL/6小鼠完全随机分为4组，即对照饲料饲喂组（MCS组）、MCD饲料饲喂组（MCD组）、对照饲料+CEL组（MCS-CEL组），MCD饲料+CEL组（MCD-CEL组），每组6只。通过MCD饮食诱导小鼠非酒精性脂肪性肝炎模型，并同时腹腔注射CEL。检测小鼠血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）含量；苏木精-伊红染色及天狼星红染色观察各组小鼠肝组织病理改变；通过代谢组学分析经CEL干预后非酒精性脂肪性肝炎小鼠的代谢特征。结果 MCD-CEL组小鼠血清ALT、AST均明显低于MCD组［（237±89）U/L比（388±70）U/L、（200±33）U/L比（454±134）U/L］，差异均有统计学意义（均P＜0.05）。病理观察显示CEL给药组小鼠肝细胞内脂肪空泡减少，炎性细胞浸润减少。代谢组学结果表明CEL可能通过调控氨基酸代谢、脂质代谢等发挥治疗非酒精性脂肪性肝炎的作用。结论 CEL可能通过调控氨基酸代谢、脂质代谢等代谢通路发挥治疗非酒精性脂肪性肝炎的作用。

• Objective To investigate the therapeutic effect and mechanism of celastrol(CEL) intervention in mice with nonalcoholic steatohepatitis induced by methionine-choline deficiency(MCD) diet. Methods Totally 24 male no specific pathogen grade C57BL/6 mice were randomly divided into 4 groups: control fodder feed group(MCS group), MCD fodder feed group(MCD group), control fodder feed+CEL intraperitoneal injection group(MCS-CEL group), MCD fodder feed+CEL intraperitoneal injection group(MCD-CEL group), with 6 mice in each group. Mouse model of non-alcoholic steatohepatitis was induced by MCD diet and intraperitoneal administration of CEL. There was detection of mouse serum alanine aminotransferase(ALT), aspartate aminotransferase(AST) content; Hematoxylin eosin staining and Sirius red staining was used to observe the pathological changes of liver tissue in each group; metabolomics analysis was used to observe the metabolic characteristics of nonalcoholic steatohepatitis mice after intervention with CEL. Results Serum ALT and AST in the MCD-CEL group were significantly lower than those in MCD group ［（237±89）U/L vs （388±70）U/L, （200±33）U/L vs （454±134）U/L］(both P＜0.05). Pathological observation showed that the fat vacuoles in the hepatocytes of the mice treated with CEL were decreased and the inflammatory cell infiltration was reduced. In addition, metabolomics results showed that CEL played a role in the treatment of nonalcoholic steatohepatitis by regulating amino acid metabolism and lipid metabolism. Conclusion CEL may play a role in the treatment of nonalcoholic steatohepatitis by regulating amino acid metabolism and lipid metabolism.