Effects of Anluohuaxianwan on transforming growth factor-β1 and related signaling pathways in rats with carbon tetrachloride-induced liver fibrosis
10.3760/cma.j.issn.1007-3418.2017.04.005
- VernacularTitle: 安络化纤丸对肝纤维化大鼠转化生长因子β1及相应信号通路的影响
- Author:
Wei LU
1
;
Yuhua GAO
1
;
Zhenzi WANG
1
;
Yushi CAI
1
;
Yuqing YANG
1
;
Yuqi MIAO
1
;
Fei PEI
2
;
Xueen LIU
1
;
Hui ZHUANG
1
Author Information
1. Department of Microbiology and Center of Infectious Diseases, Peking University Health Science Center, Beijing 100191, China
2. Department of Pathology, Basic Medical School, Peking University Health Science Center, Beijing 100191, China
- Publication Type:Journal Article
- Keywords:
Hepatic cirrhosis;
Carbon tetrachloride;
Transforming growth factor β
1;
Rat model;
Anluohuaxianwan
- From:
Chinese Journal of Hepatology
2017;25(4):257-262
- CountryChina
- Language:Chinese
-
Abstract:
Objective:The traditional Chinese medicine Anluohuaxianwan (ALHXW) has been used to treat liver fibrosis induced by chronic hepatitis B virus (HBV) infection. However, the anti-fibrosis mechanisms of ALHXW remain to be investigated. This study used a rat model of carbon tetrachloride (CCl4)-induced liver fibrosis to explore the potential antifibrogenic mechanisms of ALHXW.
Methods:Twenty-seven male Wistar rats were randomly assigned to control group, model group, and treatment group (n = 9 per group). Rats in the model and treatment group were injected intraperitoneally with 40% CCl4(2 ml/kg), and rats in the control group were administered saline twice a week for 6 weeks. Starting at week 4 following model construction, rats in the treatment group received daily gavages with ALHXW solution (concentration 0.15 g/ml) daily, while rats in the control and model groups were given saline for a total of 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured from blood samples collected at the end of weeks 3, 6 and 9. Histopathological examination of liver tissue was performed to evaluate liver fibrosis at week 9. At the same time, the mRNA expression of TGF-β1 and Smads in liver tissues was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR), and TGF-β1 protein level in the liver was measured by Western blot. Inter-group comparison was performed using analysis of variance (ANOVA) when the continuous data were normally distributed and satisfied the homogeneity of variance; otherwise, nonparametric tests were used. Categorical data were compared between groups using nonparametric tests.
Results:ALHXW markedly alleviated liver injury in the treatment group after 3 weeks of therapy as indicated by a significantly reduced level of ALT compared with the model group [(162.98 ± 73.14)U/L vs (322.52 ± 131.76)U/L, P = 0.047], and a 39.8% reduction in AST level compared with the model group[ (537.56 ± 306.06)U/L vs (892.98 ± 358.19)U/L, P = 0.053]. Moreover, at the end of the 6-week therapy, histopathological diagnosis showed that liver fibrosis was significantly reduced in the ALHXW-treated group compared with that in the model group (P = 0.002). The relative expression of TGF-β1 mRNA and protein in the liver were significantly lower in ALHXW-treated rats than that in model rats (1.34 ± 0.31 vs 1.78 ± 0.45, P = 0.025; 0.39 ± 0.02 vs 0.57 ± 0.04, P = 0.003).
Conclusion:ALHXW treatment can reverse CCl4-induced liver fibrosis in rats. Its mechanisms of anti-fibrosis may occur through the inhibition of TGF-β1 synthesis and TGF-β1/Smads signaling pathway, which in turn suppress the activation of hepatic stellate cells and thereby reverses fibrosis.
