炙甘草汤调控SIRT1/PGC-1α通路改善CCl_(4)致小鼠急性肝损伤的作用机制  

Mechanism of Fried glycyrrhizae decoction in improving CCl_(4)induced acute liver injury in mice by regulating the SIRT1/PGC-1αpathway

作　　者：李雪梅[1] 刘源[1] 乔乐天 王子亮 方明[2] LI Xuemei;LIU Yuan;QIAO Letian;WANG Ziliang;FANG Ming(Department of Pharmacy,Shangqiu First People’s Hospital,Shangqiu 476100,China;Department of Pharmacology,Shangqiu Medical College,Shangqiu 476002,China)

机构地区：[1]商丘市第一人民医院药学部,商丘476100 [2]商丘医学高等专科学校药理学教研室,商丘476002

出　　处：《天津中医药大学学报》2025年第3期226-232,共7页Journal of Tianjin University of Traditional Chinese Medicine

基　　金：河南省高等学校重点科研项目计划(24B310005)。

摘　　要：[目的]探讨炙甘草汤调控沉默信息调节因子1(SIRT1)/过氧化物酶体增殖物激活受体γ共激活剂-1α(PGC-1α)通路改善四氯化碳(CCl_(4))致小鼠急性肝损伤的作用机制。[方法]小鼠随机分为对照组、CCl_(4)组、炙甘草汤低、中、高(炙甘草汤-L、炙甘草汤-M、炙甘草汤-H)剂量(2、4、8 mL/kg)组、炙甘草汤-H+SIRT1抑制剂-sirtinol(2 mg/kg sirtinol)组、奥贝胆酸(30 mg/kg)组,除对照组外,其余各组均通过注射CCl_(4)建立小鼠急性肝损伤模型,观察小鼠一般状态及肝脏外观,收集血清,检测白细胞介素(IL)-6、丙氨酸氨基转移酶(ALT)、肿瘤坏死因子-α(TNF-α)、天冬氨酸氨基转移酶(AST)水平;收集肝脏组织,检测超氧化物歧化酶(SOD)、丙二醛(MDA)水平、病理损伤以及SIRT1/PGC-1α通路蛋白表达。[结果]与对照组相比,CCl_(4)组细胞出现坏死、炎性浸润及胶原纤维增生,血清中AST、ALT水平、TNF-α、IL-6水平、肝脏组织MDA增加,SOD、SIRT1、PGC-1α表达降低(P<0.05);与CCl_(4)组相比,炙甘草汤-L、炙甘草汤-M、炙甘草汤-H组、奥贝胆酸组病理损伤得到改善,血清中AST、ALT水平、TNF-α、IL-6水平、肝脏组织MDA降低,SOD、SIRT1、PGC-1α表达增加,不同浓度炙甘草汤差异具有统计学意义(P<0.05),但炙甘草汤-H组与奥贝胆酸组相比无差异(P>0.05);与炙甘草汤-H组相比,炙甘草汤-H+sirtinol组炎性浸润及胶原沉积增加,血清中AST、ALT水平、TNF-α、IL-6水平、肝脏组织MDA增加,SOD、SIRT1、PGC-1α表达降低(P<0.05)。[结论]炙甘草汤调控SIRT1/PGC-1α通路改善CCl_(4)致小鼠急性肝损伤。[Objective]To explore the mechanism of Fried glycyrrhizae decoction in improving carbon tetrachloride(CCl_(4))induced acute liver injury in mice by regulating the silent information regulation 1(SIRT1)/peroxisome proliferator activated receptor-gamma coactivator-1α(PGC-1α)pathway.[Methods]Mice were randomly grouped into a control group,a CCl_(4)group,a low,medium,and high(Fried glycyrrhizae decoction-L,Fried glycyrrhizae decoction-M,Fried glycyrrhizae decoction-H)dose groups(2 mL/kg,4 mL/kg,8 mL/kg),a Fried glycyrrhizae decoction-H+SIRT1 inhibitor sirtinol(2 mg/kg sirtinol)group,and obeticholic acid(30 mg/kg)group,except for the control group,all other groups established mouse acute liver injury models by injecting CCl_(4),the general state and liver appearance of mice were observed,serum was collected,and levels of interleukin-6(IL-6),alanine aminotransferase(ALT),tumor necrosis factor-α(TNF-α),and aspartate aminotransferase(AST)were detected;liver tissue was collected,and levels of superoxide dismutase(SOD),glutaraldehyde(MDA),pathological damage,and SIRT1/PGC-1αpathway protein expression were detected.[Results]Compared with the control group,CCl_(4)group cells showed necrosis,inflammatory infiltration,and collagen fiber proliferation,the levels of AST,ALT,TNF-α,IL-6 in serum,and MDA in liver tissue obviously increased,the expression of SOD,SIRT1,and PGC-1αobviously reduced(P<0.05);compared with the CCl_(4)group,the pathological damage in the Fried glycyrrhizae decoction-L,Fried glycyrrhizae decoction-M,Fried glycyrrhizae decoction-H groups,and obeticholic acid group was improved,the levels of AST,ALT,TNF-α,IL-6 in serum,and MDA in liver tissue obviously reduced,the expression of SOD,SIRT1,and PGC-1αobviously increased,different concentrations of Fried glycyrrhizae decoction showed statistical differences(P<0.05),however,there was no difference between the Fried glycyrrhizae decoction-H group and the obeticholic acid group(P>0.05);compared with the Fried glycyrrhizae decoction-H group,the Fried glycyrr

关 键 词：炙甘草汤 沉默信息调节因子1/过氧化物酶体增殖物激活受体γ共激活剂-1α通路 四氯化碳 急性肝损伤 

分 类 号：R575.3[医药卫生—消化系统]