基于UPLC-MS/MS技术的疏肝和胃汤干预慢性应激大鼠肝脏代谢组学分析  

Liver metabonomics analysis of CUMS rats intervened by Shuganheweitang based on UPLC-MS/MS

作　　者：李琦[1] 何地 周密思[1] 林云崖[1] 唐玉琼[1] 刘焱文[1] 刘松林[1] 陈新[1] LI Qi;HE Di;ZHOU Misi;LIN Yunya;TANG Yuqiong;LIU Yanwen;LIU Songlin;CHEN Xin(Hubei Key Laboratory of Resource and Chemistry of Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430065,China)

机构地区：[1]湖北中医药大学中药资源与中药化学湖北省重点实验室,湖北武汉430065

出　　处：《沈阳药科大学学报》2024年第6期686-698,共13页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(82004253);湖北省高等学校优秀中青年科技创新团队计划项(T201808)。

摘　　要：目的 基于肝脏代谢组学研究,分析疏肝和胃汤(shuganheweitang, SGHWT)对慢性应激大鼠肝组织中内源性代谢产物的影响,探究疏肝和胃汤治疗慢性应激大鼠的潜在作用机制。方法 采用慢性不可预知温和刺激(chronic unpredictable mild stress, CUMS)结合单笼饲养的方法建立慢性应激大鼠模型;利用苏木精-伊红(hematoxylin-eosin, HE)染色观察对照组(control, Con)、对照+疏肝和胃汤组(control+SGHWT,Con+SGHWT,7.33 g·kg^(-1)·d^(-1))、模型组(model, M)、模型+疏肝和胃汤组(model+SGWHT,M+SGHWT,7.33 g·kg^(-1)·d^(-1))和模型+氟西汀组(model+fluoxetine, M+F,1.58 mg·kg^(-1)·d^(-1))大鼠肝细胞的组织病理结构;运用UPLC-Q-TOF-MS/MS技术对肝组织中的内源性代谢物进行代谢组学分析,利用MetaboAnalyst在线网站进行通路分析。结果 疏肝和胃汤显著增加了慢性应激大鼠的体质量(P<0.05),糖水偏爱率(P<0.05)和旷场实验中的总移动距离(P<0.01),恢复了肝组织中肝细胞结构形态;肝脏代谢组学结果分析中共发现了51个差异代谢物发生紊乱,其中疏肝和胃汤可逆转16个内源性差异代谢物,主要涉及氨基酸代谢、能量代谢和甘油磷脂代谢。结论 疏肝和胃汤可恢复慢性应激诱导的大鼠体质量,糖水偏爱率和移动距离的减少,改善肝细胞结构,调节氨基酸代谢、能量代谢和甘油磷脂代谢。Objective A liver metabolomics study was conducted to examine the effects of Shuganheweitang(SGHWT)on endogenous metabolites in the liver tissues of chronically stressed rats to determine its potential mode of action.Methods Chronic unpredictable mild stress(CUMS)combined with single-cage feeding was used to prepare a chronic stress rat model.Hematoxylin-eosin staining was utilized to observe the histopathology structure of rat hepatocytes in the control group(Con),control+SGHWT group(Con+SGWHT,7.33 g·kg^(-1)·d^(-1)),model group(M),model+SGHWT group(M+SGWHT,7.33 g·kg^(-1)·d^(-1)),and model+fluoxetine group(M+F,1.58 mg·kg^(-1)·d^(-1)).Using UPLC-Q-TOF-MS/MS technique to perform a metabolomic study of endogenous metabolites in liver tissues and the online website of MetaboAnalyst was used for pathway analysis.Results The results showed that SGHWT significantly increased the body weight(P<0.05),sucrose preference rate(P<0.05),and total distance traveled in the open field test(P<0.01)compare with the model group,and restored the structural morphology of hepatocytes in chronically stress rats.A total of 51 differential metabolites were found to be disordered in liver metabolomic analysis.SGHWT can reverse 16 endogenous differential metabolites,which are mainly involved in amino acid metabolism,energy metabolism,and glycerophospholipid metabolism.Conclusion SGHWT enhances hepatocyte structure and reverses the chronic stress-induced reduction of body weight,sucrose preference rate,and total movement distance.It also exhibition an antidepressant effect by regulating amino acid metabolism,energy metabolism,and glycerophospholipid metabolism.

关 键 词：疏肝和胃汤 CUMS 肝脏代谢组学 UPLC-MS/MS 

分 类 号：R28[医药卫生—中药学] R96[医药卫生—中医学] R917