中药新药与临床药理2025，Vol.36Issue(5)：692-702,11.DOI:10.19378/j.issn.1003-9783.2025.05.005
虎金方通过SIRT1调节线粒体功能改善代谢相关脂肪性肝病的机制
Mechanism of Hujin Formula in Improving MAFLD by Regulating Mitochondrial Function via SIRT1
摘要
Abstract
Objective To investigate the mechanism by which Hujin Formula improves metabolic-associated fatty liver disease(MAFLD)by regulating mitochondrial function through silent information regulator 1(SIRT1).Methods A MAFLD mouse model was established using a high-fat diet.The mice were randomly divided into a normal group,a model group,a low-dose Hujin Formula group(5.31 g·kg-1),a high-dose Hujin Formula group(21.24 g·kg-1),a Silibinin group(12 mg·kg-1),an EX-527 group(10 mg·kg-1),an EX-527+low-dose Hujin Formula group,an EX-527+high-dose Hujin Formula group,and an EX-527+Silibinin group.The treatment groups were administered by gavage for 4 weeks,while EX-527 was injected twice weekly for 4 weeks.Body mass and liver mass were recorded.Liver tissue was observed using HE staining and Oil Red O staining.Serum levels of triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)were measured.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),reactive oxygen species(ROS),and adenosine triphosphate(ATP)in liver tissue were detected.Western Blot was used to measure the protein expression levels of SIRT1,peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α),nuclear respiratory factor 1(NRF1),and transcription factor A,mitochondrial(TFAM)in liver tissue.Results Compared with the normal group,the model group showed significantly increased body mass and liver mass(P＜0.01),disordered liver tissue structure,and increased fat vacuoles.Serum levels of TG,TC,LDL-C,AST,ALT,TNF-α,and IL-6,as well as MDA levels in liver tissue,were significantly elevated(P＜0.000 1),while ATP content was significantly reduced(P＜0.000 1).Protein expression of SIRT1,PGC-1α,NRF1,and TFAM was significantly downregulated(P＜0.000 1).Compared with the model group,treatment groups showed significantly reduced body mass and liver mass(P＜0.01,P＜0.001,P＜0.000 1),improved liver tissue structure,and decreased fat vacuoles.Serum levels of TG,TC,LDL-C,AST,ALT,TNF-α,and IL-6,as well as MDA levels in liver tissue,were significantly reduced(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1),while ATP content was significantly increased(P＜0.01,P＜0.001).Protein expression of SIRT1,PGC-1α,NRF1,and TFAM was significantly upregulated(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1),with a dose-dependent effect observed in the Hujin Formula groups.Compared with the model group,the EX-527 group(SIRT1 inhibitor group)exhibited more disordered liver tissue structure,larger and more numerous fat vacuoles,and more severe red staining.TNF-α,IL-6,and MDA levels were significantly elevated(P＜0.05,P＜0.000 1),ATP content was significantly reduced(P＜0.000 1),and protein expression of SIRT1 was significantly downregulated(P＜0.000 1).Compared with the EX-527 group,the EX-527+low-dose Hujin Formula group,EX-527+high-dose Hujin Formula group,and EX-527+Silibinin group showed significantly reduced body mass and liver mass(P＜0.01,P＜0.001),more orderly hepatocyte arrangement,and significantly fewer fat vacuoles.Serum levels of TG,TC,TNF-α,and IL-6,as well as MDA levels in liver tissue,were significantly reduced(P＜0.05,P＜0.01,P＜0.001),while ATP content was significantly increased(P＜0.000 1).SIRT1 protein expression was significantly upregulated in the EX-527+high-dose Hujin Formula group and EX-527+Silibinin group(P＜0.05).Conclusion Hujin Formula may improve mitochondrial function,promote lipid metabolism,and alleviate liver inflammation and oxidative stress by upregulating SIRT1,thereby delaying the progression of MAFLD.关键词
虎金方/代谢相关脂肪性肝病/沉默信息调节因子1/线粒体功能/小鼠Key words
Hujin Formula/metabolic-associated fatty liver disease/silent information regulator 1/mitochondrial function/mice分类
医药卫生引用本文复制引用
施家希,刘付轩,张梓煊,沈淇,吴伟,施旭光..虎金方通过SIRT1调节线粒体功能改善代谢相关脂肪性肝病的机制[J].中药新药与临床药理,2025,36(5):692-702,11.基金项目
广东省自然科学基金项目(2022A1515012265). （2022A1515012265）
