Effects of tanshinoneIIA on cardiac hypertrophy in rats

Abstract

Objective To explore the effects and mechanisms of tanshinone ⅡA (Tan ⅡA) on cardiac hypertrophy in rats. Methods 40 SD rats of 2-3 months old were randomly divided into four groups with 10 in each group, transverse aortic constriction (TAC) was used to simulate pressure-overload models. The four groups were handled as follows, the sham group rats just underwent laparotomy; the surgery group were exposed to TAC as TAC group; the Tan ⅡA group rats were administered Tan ⅡA (20 mg·kg-1·d-1) by intraperitoneal injection for 8 weeks after TAC; the negative control group rats were given normal saline (20 mg·kg-1·d-1) by intraperitoneal injection for 8 weeks after TAC. After 8 weeks of TAC, we randomly chose 6 rats from each group and anaesthetized them. Echocardiogram was performed to evaluate cardiac structure and function. After measuring body weight, the chosen rats were dissected and their heart weight were measured to calculate heart-weight index (HWI). The acquired heart tissue was used to produce frozen sections performed with hematoxylin and eosin (HE) staining and Masson staining to evaluate cell surface area (CSA) and collagen volume fraction (CVF), respectively. Western blot analysis was performed to evaluate calcium/calmodulin-dependent protein kinase Ⅱ(CAMK Ⅱ) and calcineurin (CaN) protein expression in rat heart tissue. Results Compared to TAC group, Tan Ⅱ A group rats had lower left ventricular posterior wall thickness (LVPWd) and interventricular septum thickness (IVSd) [LVPWd: (0.2±0.01) cm vs (0.22±0.01) cm, P<0.05; IVSd: (0.18±0.02) cm vs (0.22±0.02) cm, P<0.05]. HWI was also lower in TanⅡA group compared with TAC group [(43.43±5.10) mg/g vs (49.38±3.80) mg/g, P<0.05]. The staining results showed Tan Ⅱ A significantly inhibited myocardial hypertrophy and fibrosis caused by TAC[CSA: (555.48±879.81) μm2 vs (514.74±1281.16) μm2, P<0.05;CVF: (8.63%±2.26% vs 12.39%±1.90%, P<0.05)]. Western blot analysis demonstrated that Tan ⅡA could reduce the elevation of CAMK Ⅱ and CaN protein expression resulted from TAC[CAMKⅡ: (1.2±0.1) vs (1.83±0.25), P<0.05;CaN: (1.27±0.12) vs (1.93±0.49), P<0.05]. Conclusion TanshinoneⅡA could inhibit pressure-overload induced myocardial hypertrophy in rats. Key words: Myocardial hypertrophy; TanshinoneⅡA; Transverse aortic constriction