Toll-Like Receptor 3 Gene Deficiency Aggravates Carbon Tetrachloride-Induced Liver Fibrosis in Mice
- VernacularTitle:Toll样受体3基因缺陷促进四氯化碳诱导的小鼠肝纤维化损伤
- Author:
Ruyi UE X
1
;
Danying NG ZHA
;
Hao WU
;
Taotao LIU
;
Ling DONG
;
Xizhong SHEN
Author Information
1. 复旦大学附属中山医院消化内科
- Keywords:
Toll-like receptor 3;
Mouse with Gene deficiency;
Carbon tetrachloride;
Liver fibrosis
- From:
Chinese Journal of Clinical Medicine
2016;23(1):1-5
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of Toll‐like receptor 3(TLR3) gene deficiency on the degree of liver fibrosis in mouse model of carbon tetrachloride(CCl4 )‐induced liver fibrosis .Methods :A total of 20 wild‐type male mice and 20 male mice with TLR3 gene deficiency (TLR3‐/‐) were divided into wild‐type control group and wild‐type model group ,TLR3‐/‐ control group and TLR3‐/‐ model group ,respectively ,with 10 mice in each group .The control group was injected with corn‐oil by intraperitoneal injection while the model group was injected with CCl4 by intraperitoneal injection .After 8 weeks ,blood sample wascollectedandserumlevelofalanineaminotransferase(ALT),aspartatetransaminase(AST),totalbilirubin(TBIL),and albumin(Alb) was analyzed by automatic biochemical analyzer .And the degree of collagen deposition in liver tissue was evaluated by Masson trichrome staining .And the activation of hepatic stellate cells was detected by immunohistochemistry staining of α‐smooth muscle actin(α‐SMA).And hydroxyproline content of liver tissue was detected with detection kit . Furthermore ,real‐time fluorescence polymerase chain reaction was used to detect the expression of liver fibrotic marker type I collagen ,and inflammatory cytokines including tumor necrosis factor‐alpha (TNF‐α) , interleukin‐6 (IL‐6 ) and monocyte chemotactic protein‐1(MCP‐1) ,as well as pro‐fibrotic molecule including transforming growth factor‐beta (TGF‐β) ,tissue inhibitor of metalloproteinase 1(TIMP1) and platelet‐derived growth factor receptor(PDGFR) .Results:TLR3 gene deficiency had no effect on CCl4‐induced change regarding serum level of ALT ,AST ,TBIL ,ALB .TLR3 gene deficiency aggregated the CCl4‐induced collagen deposition and hepatic stellate cell activation in liver tissue .And it promoted the CCl4‐induced elevation of hydroxyproline content and expression increase of fibrotic marker type I collagen .Furthermore ,the expression increase of inflammatory cytokines including TNF‐α,IL‐6 and MCP‐1 ,as well as that of pro‐fibrotic molecule including TGF‐β,TIMP1 and PDGFR ,was promoted .Conclusions :TLR3 gene deficiency could promote liver collagen deposition and hepatic stellate cell activation in mouse model of CCl4‐induced liver fibrosis ,and it could promote inflammatory cytokine release and pro‐fibrotic molecule up‐regulation .All above suggest that TLR3 is a protective gene during liver fibrosis pathological process .
