Simvastatin augments activation of liver regeneration through attenuating transforming growth factor‑β1 induced‑apoptosis in obstructive jaundice rats

Fang,Dazheng; He,Ying; Luan,Zhou

doi:10.3892/etm.2017.5156

Simvastatin augments activation of liver regeneration through attenuating transforming growth factor‑β1 induced‑apoptosis in obstructive jaundice rats

Authors:
- Dazheng Fang
- Ying He
- Zhou Luan
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Affiliations: Department of Hepatobiliary Surgery, Dongfeng General Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China, Department of Ophthalmology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China, Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: September 21, 2017 https://doi.org/10.3892/etm.2017.5156
Pages: 4839-4845
Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Obstructive jaundice, owing to biliary obstruction, has been illustrated to trigger various biochemical, histological and immunological changes, leading to liver damage or even failure. The detailed molecular mechanism of simvastatin (Sim) involvement in liver regeneration during obstructive jaundice progression remains poorly elucidated. In the present study, an acute obstructive jaundice rat model was established by ligation and division of common bile duct, which was used to investigate the effects of Sim as a hepatoprotective treatment. Male Sprague‑Dawley rats were randomly divided into four groups: Sham‑operated, bile duct ligation (BDL) plus saline treatment [0.02 mg/kg/d, intraperitoneally (i.p.)], BDL plus low‑dose Sim treatment (0.02 mg/kg, i.p.) and BDL plus high‑dose Sim treatment (0.2 mg/kg, i.p.). During this experiment, the BDL+normal saline (NS) group demonstrated increased levels of transforming growth factor‑β1 (TGF‑β1) expression. Furthermore, Sim‑treated animals demonstrated significantly downregulated TGF‑β1 expression and improved liver function vs. the BDL+NS group, indicating a TGF‑β1 antagonizing function. Additionally, Sim increased hepatocyte DNA synthesis in BDL rats compared to both the BDL+NS and Sham group. Apoptosis was increased in BDL+NS compared to the Sham group, and Sim markedly reduced hepatocyte apoptosis in the BDL group. Moreover, analysis of TGF‑β1 signaling pathways demonstrated that there was an increased hepatic TGF‑β1 and Smad3 expression in the BDL group, which was attenuated in the presence of Sim. In contrast to TGF‑β1, Sim induced the activity of the Smad7 (an inhibitor of TGF‑β1 signaling) mRNA and Smad7 protein expression. Sim displays hepatoprotective effects in liver cells via the upregulation of Smad7 expression and impaired TGF‑β signaling. Furthermore, the observations of the present study may provide evidence on the mechanism behind Sim blunting TGF‑β1 signaling, which is used to ameliorate the complication of liver damage and reduce the mortality rates associated with obstructive jaundice.

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