中国实验动物学报2024，Vol.32Issue(5)：630-637,8.DOI:10.3969/j.issn.1005-4847.2024.05.010
虫草菌丝调节AMPK/SirT1信号通路对四氯化碳诱导肝纤维化小鼠的作用
Effects of cultured mycelium Cordyceps sinensis on carbon tetrachloride-induced liver fibrosis mice by regulating AMPK/SirT1 signaling pathway
摘要
Abstract
Objective To investigate the effects of cultured mycelium Cordyceps sinensis(CMCS)on the AMPK/SirT1 signaling pathway in carbon tetrachloride(CCl4)-induced liver fibrosis in mice.Methods Forty male SPF-grade C57BL/6 mice were divided randomly into a normal control group,CMCS control group(3.0 g/kg),model control group,CMCS1.5 g/kg group,and CMCS 3.0 g/kg group.Mice were injected intraperitoneally with 10%CCl4(2 mL/kg)to induce liver fibrosis.Two weeks later,serum levels of alanine transaminase(ALT),aspartate transaminase(AST),and total bilirubin(TBil)were measured.Inflammation and collagen deposition in liver tissue were observed by hematoxylin and eosin(HE)and Sirius red staining,respectively.The content of hydroxyproline in liver tissue was detected by Jamall's hydrochloric acid hydrolysis method.Levels of interleukin(IL)-6,monocyte chemoattractant protein-1(MCP-1),interferon,tumor necrosis factor(TNF),IL-10,and IL-12p70 in liver tissue were detected using a cytometric bead array analysis system.Collagen Ⅰ and SirT1 expression in liver tissue were detected by immunohisotochemistry,and Prkaa1,Prkaa2,Lkb1,and p53 gene expression were detected by real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction.Results Serum levels of ALT,AST,and TBil were significantly increased in the model control group compared with those in the normal control group(P＜0.05).HE and Sirius red staining showed extensive inflammatory cell infiltration and collagen deposition in the liver,respectively.Hydroxyproline content and expression levels of IL-6,MCP-1,and TNF in the liver were significantly increased(P＜0.05),while IL-10 and IL-12p70 levels were significantly decreased(P＜0.01).Immunohistochemical staining revealed an increase in Collagen Ⅰ expression and SirT1 staining was decreased in the hepatic sinusoidal space,while collagen deposition was increased.Prkaa1,Prkaa2,and Lkb1 gene expression levels were decreased and p53 was increased in liver tissue(P＜0.05).CMCS significantly reduced serum ALT and AST levels,decreased IL-6,MCP-1,and TNF expression in liver tissue(P＜0.05),up-regulated IL-10 and IL-12p70(P＜0.05),alleviated liver inflammation,collagen deposition,and hydroxyproline content,up-regulated the expression of SirT1 in the hepatic sinusoidal space,enhanced Prkaa1,Prkaa2,and Lkb1 expression(P＜0.05),and down-regulated Collagen Ⅰ and p53(P＜0.05)in the liver.Compared with CMCS 1.5 g/kg,CMCS 3.0 g/kg significantly inhibited liver inflammation and collagen deposition and up-regulated AMPK/SirT1 expression(P＜0.05).Conclusions CMCS could improve CCl4-induced liver fibrosis via up-regulation of the AMPK/SirT1 signaling pathway.关键词
虫草菌丝/四氯化碳(CCl4)/肝纤维化/AMPK/SirT1信号通路Key words
cultured mycelium Cordyceps sinensis/carbon tetrachloride/liver fibrosis/AMPK/SirT1 signaling pathway分类
生物科学引用本文复制引用
杨钊,闫阮玉,吴洪雨,黄恺,沈丽,陶艳艳,刘成海,彭渊..虫草菌丝调节AMPK/SirT1信号通路对四氯化碳诱导肝纤维化小鼠的作用[J].中国实验动物学报,2024,32(5):630-637,8.基金项目
国家自然科学基金(81102701,81874363,82174057,82274305),山西中医药大学科技创新团队项目(2022TD2003),曙光四明学者计划(SGXZ-201910).Funded by National Natural Science Foundation of China(81102701,81874363,82174057,82274305),Science and Technology Innovation Team Project of Shanxi University of Traditional Chinese Medicine(2022TD2003),Shuguang Siming Scholar Plan(SGXZ-201910). （81102701,81874363,82174057,82274305）
