The Salvia miltiorrhiza monomer IH764-3 induces apoptosis of hepatic stellate cells in vivo in a bile duct ligation-induced model of liver fibrosis

Liu,Lei; Wei,Juan; Huo,Xiaoxia; Fang,Shuming; Yao,Dongmei; Gao,Junping; Jiang,Huiqing; Zhang,Xiaolan

doi:10.3892/mmr.2012.1076

The Salvia miltiorrhiza monomer IH764-3 induces apoptosis of hepatic stellate cells in vivo in a bile duct ligation-induced model of liver fibrosis

Authors:
- Lei Liu
- Juan Wei
- Xiaoxia Huo
- Shuming Fang
- Dongmei Yao
- Junping Gao
- Huiqing Jiang
- Xiaolan Zhang
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Affiliations: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei 050000, P.R. China, Department of Hepatology, The Fifth Hospital of Shijiazhuang City, Hebei 050021, P.R. China, Department of Gastroenterology, The Third Hospital of Shijiazhuang City, Hebei 050011, P.R. China
Published online on: September 11, 2012 https://doi.org/10.3892/mmr.2012.1076
Pages: 1231-1238

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Abstract

During the process of liver fibrosis, hepatic stellate cells (HSCs) play a critical role in the excessive production of extracellular matrix (ECM). Previous studies have indicated that the monomer IH764-3, one of the major bioactive components of Salvia miltiorrhiza, is able to inhibit HSC proliferation and induce the apoptosis of activated HSCs in vitro. In the current study, we used a rat model of liver fibrosis induced by bile duct ligation (BDL) to investigate the effect of the monomer IH764-3 on the induction of apoptosis in HSCs in vivo. The rat model of liver fibrosis was established by BDL. Immunohistochemical staining of α-smooth muscle actin (α-SMA) was performed to detect HSC activation and proliferation and HSC apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and α-SMA immunohistochemical double staining. In addition, the protein expression levels of focal adhesion kinase (FAK), p-FAK (Tyr397), extracellular signal-regulated kinase (ERK) and p-ERK and the mRNA expression levels of FAK and ERK were measured by western blotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The monomer IH764-3 was associated with a significant decrease in intrahepatic fibrogenesis and collagen deposition and attenuated the liver fibrosis induced by BDL. Immunohistochemical staining revealed that the expression of α-SMA in the IH764-3 group was significantly decreased compared with that in the model group (12.92±2.45 vs. 22.65±2.16%, P<0.01). TUNEL and α-SMA immunohistochemical double staining also confirmed that IH764-3 increased the apoptotic rate of the activated HSCs (34.8±4.5 vs. 4.72±0.37%, P<0.01). Moreover, the results revealed that IH764-3 downregulated the expression levels of FAK, p-FAK (Tyr397), ERK and p-ERK in the liver tissue of rats with liver fibrosis. The monomer IH764-3 ameliorates experimental liver fibrosis by inhibiting HSC proliferation and inducing HSC apoptosis, warranting its use as a potential therapeutic agent in the treatment of liver fibrosis.

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