Matrine ameliorates isoproterenol-induced acute myocardial ischemia through regulation of growth factors and RhoA/ROCK1 pathway

Growth factors and inflammatory Ras homolog gene family member A (RhoA)/coiled-coil containing protein kinase 1 (ROCK1) pathway have been shown to regulate isoproterenol (ISO)-induced myocardial ischemia. However, the association between matrine and myocardial ischemia remains to be elucidated. The objective of this study was to explore whether matrine ameliorates ISO-induced myocardial ischemia through modulating growth factors and RhoA/ROCK1 cell signaling. Male Sprague-Dawley rats were pretreated with matrine (50, 100 and 200 mg/kg/d) intragastrically for two days. Acute myocardial ischemia was induced in rats by subcutaneous injection of ISO (85 mg/ kg/d) for two days. Histopathological changes, cardiac troponin (cTn-I) levels, mRNA and/or protein levels of growth factors, collagen 1a1 and 3a1 and RhoA/ROCK1 were measured. Short-term oral administration of matrine provided protection against ISO-induced acute myocardial ischemia. Matrine reduced ISO-induced cTn-I (from 50.43±1.79 to 35.99±3.23, P < 0.01) and collagen 1a1 (from 0.30±0.09 to 0.13±0.10, P < 0.05), and reversed ISO-induced suppression of transforming growth factor-beta1 (TGF-β1) (from 24.07±6.17 to 51.59±6.50, P < 0.05), insulinlike growth factor-1 (IGF-1) (from 97.73±24.19 to 146.83±37.20, P < 0.01). Meanwhile, it prevented ISO-induced increases in RhoA (from 0.311±0.042 to 0.124±0.031, P < 0.01)/ROCK1 (from 0.305±0.019 to 0.171±0.010, P < 0.05). Taken together, the cardioprotective effect of matrine on ISO-induced myocardial ischemia is associated with its ability of increasing levels of the IGF-1, TGF-β1, suppressing cTn-I release and inflammatory mediators RhoA/ ROCK1. Therefore, matrine may be a potential medication for the treatment of myocardial ischemia.