Effects of Kangxian Ruangan Granules on TGF-β1/Smad Signaling Pathway in Mice with Liver Fibrosis
10.19879/j.cnki.1005-5304.202503591
- VernacularTitle:抗纤软肝颗粒对肝纤维化小鼠TGF-β1/Smad信号通路的影响
- Author:
Zhiwei SU
1
;
Yuxue DING
;
Jun SUN
;
Chunyan JI
;
Juan XUE
Author Information
1. 湖北中医药大学,湖北 武汉 430065
- Publication Type:Journal Article
- Keywords:
Kangxian Ruangan Granules;
liver fibrosis;
TGF-β1/Smad signaling pathway;
mice
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2025;32(11):84-91
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the mechanism of Kangxian Ruangan Granules in improving mouse liver fibrosis by regulating TGF-β1/Smad signaling pathway.Methods Eight out of 50 SPF grade male C57BL/6J mice were randomly selected as the normal group,and the remaining mice were intraperitoneally injected with 20%CCl4 olive oil solution(2 mL/kg,3 times a week for 4 weeks)to establish the liver fibrosis model.The successfully modeled mice were randomly divided into model group,silibinin group,and Kangxian Ruangan Granules low-,medium-and high-dosage groups using a random number table method,with 8 mice in each group.Each group of Kangxian Ruangan Granules was orally administered at dosages of 1.95,3.90 and 7.80 g/kg;the silibinin group was orally administered at a dosage of 100 mg/kg,while the normal group and model group were given equal volume of physiological saline by gavage,once a day for 8 weeks.The body mass and liver mass of mice were weighed and the liver index was calculated,the contents of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),hydroxyproline(HYP),hyaluronic acid(HA),type Ⅲ procollagen(PC-Ⅲ),type Ⅳ collagen(ColⅣ)and laminin(LN)were detected by ELISA;liver tissue morphology was observed using HE,Masson and sirius red staining;immunohistochemistry,RT-qPCR and Western blot were used to detect the expressions of type Ⅰ collagen(ColⅠ),α-smooth muscle actin(α-SMA)and TGF-β1/Smad signaling pathway related factors in liver tissue.Results Compared with the normal group,the body mass of the model group mice decreased(P<0.01),while the liver mass and liver index increased(P<0.01);the contents of ALT,AST,HYP,HA,LN,PC-Ⅲ and ColⅣ were increased(P<0.01);the structure of liver lobules was disordered,with diffuse steatosis of liver cells,disordered arrangement of hepatic cords,infiltration of inflammatory cells,and significant fibrosis in the central and portal vein areas of liver lobules;the mRNA expressions of TGF-β1,Smad2 and Smad3 in liver tissue increased(P<0.05,P<0.01),and the protein expressions of ColⅠ,α-SMA,TGF-β1,Smad2,Smad3,p-Smad2 and p-Smad3 increased(P<0.05,P<0.01).Compared with the model group,the body mass of mice in silibinin group and each dosage of Kangxian Ruangan Granules increased(P<0.01),while the liver mass and liver index decreased(P<0.01);the contents of ALT,AST,HYP,HA,LN,PC-Ⅲ and ColⅣ in serum decreased(P<0.01);the hepatic steatosis in mice was reduced,the necrotic area was narrowed,the infiltration of inflammatory cells was reduced,the arrangement of hepatic cords tended to be regular,collagen deposition was reduced,and the structure of liver lobules was partially restored;the mRNA expressions of TGF-β1,Smad2 and Smad3 in liver tissue of silibinin group and Kangxian Ruangan Granules medium-dosage group decreased(P<0.05,P<0.01),while the protein expression of ColⅠ,α-SMA,TGF-β1,Smad2,Smad3,p-Smad2 and p-Smad3 decreased(P<0.05,P<0.01).Conclusion Kangxian Ruangan Granules can reduce the expressions of fibrosis related proteins,inhibit the deposition of extracellular matrix and improve liver fibrosis by inhibiting TGF-β1/Smad signaling pathway.