Protective effect of oxymatrine on myocardial fibrosis induced by acute myocardial infarction in rats involved in TGF-β₁-Smads signal pathway

Abstract

Oxymatrine (1), a component extracted from a traditional Chinese herb Sophora japonica (Sophora flavescens Ait.), has been demonstrated to have a variety of pharmacological actions. Abundant experimental evidence indicates that 1 may exert a protective effect on the cardiovascular system. This study was designed to explore the possible role of 1 against myocardial fibrosis induced by acute myocardial infarction (AMI) and its modulation on transforming growth factor beta 1 (TGF-β₁)-Smads signaling pathways. Rats with AMI induced by ligation of left anterior descending branch were randomly assigned to receive 1 50 and 25 mg/kg intragastrically, and model group which were further compared with sham-operated group, and positive group treated with captopril. The effects of 4-week therapy with 1 starting 24 h after infarction had been investigated based on (1) hemodynamics, (2) tissue weights, (3) biochemical indicator (hydroxyproline contents in left ventricle), and (4) TGF-β₁, TGF-β₁ receptor (TβR₁), Smad3, Smad4, Smad7, Col1, and Col3 expression by semi-quantitative reverse transcription PCR. Treatment with 1 significantly ameliorated hemodynamics, inhibited the expression of TβR₁ mRNA and Smad3 mRNA, and reduced the left ventricle weight/body weight. The results of this research indicated that 1 might protect against myocardial fibrosis and the mechanism may be involved in modulating TGF-β₁-Smads signal pathway.

Keywords:

• oxymatrine
• acute myocardial infarction
• cardiac fibrosis
• TGF-β₁-Smads signal

Acknowledgements

This research was supported by a grant from National Natural Science Foundation of China (No. 30701024), Provincial Key Technologies R&D Program of Guizhou (No. 2007-1035), International Science and Technology Exchange and Cooperation of Guizhou Province (No. 2009-700115), and Foundation for Open Projects of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica (No. P09003). The authors are grateful to Associate Prof. Qi-hong Fu for valuable comments on the manuscript.