Amelioration of cardiac dysfunction and ventricular remodeling after myocardial infarction by danhong injection are critically contributed by anti-TGF-β-mediated fibrosis and angiogenesis mechanisms

Abstract

Ethnopharmacological relevance: Danhong injection (DHI) is a standardized product extracted from Radix et Rhizoma Salviae Miltiorrhizae and Flos Carthami , which has been long applied mainly used to treat ischemic encephalopathy and cardiac diseases including myocardial infarction and angina in clinical practice.

Aim of the study: Aim of this study was to investigate the salutary effects of DHI by slowing ventricular remodeling and improving cardiac function after myocardial infarction (MI) in rats.

Materials and methods: In this study, Male Sprague-Dawley rats were subjected to ligation on left anterior descending coronary artery to establish MI models and valsartan was selected as positive control. Cardiac function examination was conducted at the 1st, 3rd, 7th, 14th and the 28th days after LAD. Haematoxylin and Eosin (HE) staining and Masson staining were conducted to observe cardiac pathology and morphological changes levels of VEGF, TGF-β, MMP-2, and MMP-9 in the myocardial tissue were determined in gene and protein expressions.

Results: After 3 days post-treatment and thereafter, EF and FS in DHI group were greater than that of model group (p<0.05). Compared with the MI group, ratio of infarct was markedly decreased in treated-DHI group(p<0.05). TGF-β1 protein and fibrosis-related proteins MMP-2 and MMP-9 were up-regulated after MI, and they were significantly suppressed by the administration of DHI(p<0.05 and p<0.01, respectively). Moreover, DHI improved the mRNA expression of VEGF and increased the blood vessel density of myocardial infarct border zone. DHI decreased the expression of cell apoptosis protein of caspase-3 and increased the anti-apoptotic protein, bcl-2.

Conclusions: We provided direct evidences that DHI improves cardiac remodeling and preserves ventricular function post-MI in rats. DHI conferred cardio-protection in rats with MI via anti-myocardial apoptosis, angiogenesis, reduction of myocardial fibrosis and many other aspects of joint actions.

Keywords: Angiogenesis; Anti-myocardial apoptosis; Cardiac function; Danhong injection; Ventricular remodeling.