Carvedilol improves liver cirrhosis in rats by inhibiting hepatic stellate cell activation, proliferation, invasion and collagen synthesis

Ling,Liping; Li,Guangqi; Wang,Guangchuan; Meng,Dongxiao; Li,Zhen; Zhang,Chunqing

doi:10.3892/mmr.2019.10401

Carvedilol improves liver cirrhosis in rats by inhibiting hepatic stellate cell activation, proliferation, invasion and collagen synthesis

Authors:
- Liping Ling
- Guangqi Li
- Guangchuan Wang
- Dongxiao Meng
- Zhen Li
- Chunqing Zhang
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Affiliations: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Oncology, Binzhou People's Hospital, Binzhou, Shandong 256603, P.R. China
Published online on: June 20, 2019 https://doi.org/10.3892/mmr.2019.10401
Pages: 1605-1612
Copyright: © Ling et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Portal hypertension (PHT) is one of the most severe consequences of liver cirrhosis. Carvedilol is a first‑line pharmacological treatment of PHT. However, the antifibrogenic effects of carvedilol on liver cirrhosis and the intrinsic mechanisms underlying these effects have not been thoroughly investigated. The present study aimed to investigate the antifibrogenic effects of carvedilol on liver cirrhosis in vivo and in vitro. Liver cirrhosis was induced in rats by carbon tetrachloride (CCl4) administration for 9 weeks; carvedilol was administered simultaneously in the experimental group. Blood samples were collected for serum biochemistry. Liver tissues were used for fibrosis evaluation, histological examination, immunohistochemistry and western blot analysis. The human hepatic stellate cell (HSC) line LX‑2 was used for in vitro studies. The effects of carvedilol on LX‑2 cell proliferation and invasion were evaluated by Cell Counting Kit‑8 assay and Transwell invasion assays, respectively. The effect of carvedilol on transforming growth factor β1 (TGFβ1)‑induced collagen synthesis in LX‑2 cells and the molecular mechanisms were examined by western blot analysis. The results demonstrated that carvedilol improved CCl4‑induced structural distortion and fibrosis in the liver. Carvedilol inhibited HSC activation, proliferation and invasion. Carvedilol inhibited HSC collagen synthesis through the TGFβ1/SMAD pathway. In conclusion, carvedilol may alleviate liver cirrhosis in rats by inhibiting HSC activation, proliferation, invasion and collagen synthesis. Carvedilol may be a potential treatment of early‑stage liver cirrhosis.

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