炙甘草汤调控SIRT1/PGC-1α通路改善CCl4致小鼠急性肝损伤的作用机制

Mechanism of Fried glycyrrhizae decoction in improving CCl4 induced acute liver injury in mice by regulating the SIRT1/PGC-1α pathway

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

Key words:  Fried glycyrrhizae decoction  SIRT1/PGC-1α pathway  CCl₄  acute liver injury

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（CCl₄）致小鼠急性肝损伤的作用机制。[方法] 小鼠随机分为对照组、CCl₄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CCl₄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，CCl₄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CCl₄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CCl₄致小鼠急性肝损伤。

Abstract:

[Objective] To explore the mechanism of Fried glycyrrhizae decoction in improving carbon tetrachloride(CCl₄) 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 CCl₄ 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 CCl₄,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-1α pathway protein expression were detected. [Results] Compared with the control group,CCl₄ 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-1α obviously reduced(P＜0.05);compared with the CCl₄ 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-1α obviously 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 glycyrrhizae decoction-H+sirtinol group showed an increase in inflammatory infiltration and collagen deposition,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-1α obviously reduced(P＜0.05). [Conclusion] Fried glycyrrhizae decoction regulates the SIRT1/PGC-1α pathway to improve CCl₄ induced acute liver injury in mice.