| Left ventricular remodeling (LVR) is the process by which ventricular size, shape, and function are regulated by mechanical, neurohormonal, and genetic factors after myocardial infarction (MI). Myocardial fibrosis (MF) is a characteristic feature of LVR that is directly related to myocardial hypertrophy and heart failure (HF). According to the clinical studies, LVR process affects the short-term and long-term prognosis of MI. Cytokine transforming growth factor-β1 (TGF-β1) can promote the deposition of extracellular matrix (ECM), which is believed to have essential role in the process of fibrosis. Tranilast (N-[3,4-dimethoxycinnamoyl] anthranilic acid), a drug originally used for treatment of allergic and dermatological diseases, was found to inhibit TGF-β1-madiated collagen formation. In some experimental animal studies, tranilast has been shown to reduce pathological collagen accumulation in the myocardium of hypertensive rat.Based on the anti-TGF-β1-madiated fibrosis mechanism of tranilast, the following experimental study is designed. The objective is to observe the effect of tranilast on myocardial fibrosis and expression of transforming growth factor-β1 protein in the non-infarcted myocardium after myocardial infarction in rats.MI model was established in male Wister rats by ligation of left anterior descending coronary artery. Forty-eight hours after the procedure, the survived rats were randomly divided into three groups: sham-operated group (n=10), MI model group (n=12) and Tranilast treatment group (n=13). Sham-operated rat only undergo pericardiotomy without coronary artery ligation. Rats of tranilast treatment group received a daily dose of 400mg/kg by intragastric administration in normal saline administered as 200mg/kg twice daily while untreated rats were gavaged with vehicle. After 4 weeks of treatment, the cardiac function was assessed by hemodynamic measurements before the rats were sacrificed, and left ventricular weight was measured. The heart histology and morphology was observed with HE stain. Infarct size in the infarct region was measured with previous experimental method. The expression of TGF-β1 was detected by immunohistochemical technique. The hydroxyproline level of left ventricle non-infarcted area was measured by chloramines T method.Result showed that compared with sham-operated rats, the left ventricular end-diastolic pressure (LVEDP), the ratio of left ventricular weight and body weight, TGF-β1 expression and hydroxyproline level in MI model group were significantly increased (all P< 0.01), while the LV systolic pressure (LVSP), the maximum left ventricular pressure rising and dropping rates (±dP/dt) were significantly reduced (all P < 0.01). Compared with the MI model group, tranilast did not decrease infarct size (P > 0.05), but it did decrease LVEDP, the ratio of left ventricular weight and body weight, TGF-β1 expression and HYP level (P < 0.05), and increased±dP/dt significantly (P < 0.05). These results showed tranilast can inhibit myocardial fibrosis through decreasing the expression of TGF-β1, and improve left ventricular function after MI in rats.From this study, we could have a deeper understanding about the effect of tranilast on myocardial fibrosis and expression of TGF-β1 after MI in rats. In conclusion, our researches can offer some referenced and theoretic proof for the clinic use which target tranilast.
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