Journal
MOLECULAR MEDICINE REPORTS
Volume 6, Issue 6, Pages 1231-1238Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2012.1076
Keywords
Salvia miltiorrhiza monomer IH764-3; liver fibrosis; hepatic stellate cells; proliferation; apoptosis
Categories
Funding
- Department of Science and Technology of Hebei Province [09966107D]
- Traditional Chinese Medicine Drug Administration of Hebei Province [2007061]
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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 a-smooth muscle actin (alpha-SMA) was performed to detect HSC activation and proliferation and HSC apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and a-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 a-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 a-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 FA K, 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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