ASSA14-03-02 Protective Effects of Paeoniflorin against Myocardial Fibrosis in Isoprenaline-induced Chronic Heart Failure Rats

Abstract

<h3>Background</h3> The life time risk of developing heart failure is 20% for Americans over 40 years old. Chronic heart failure (CHF) is becoming a global health problem in the elderly. Previous studies indicate that immune-inflammatory activation plays an important role in the pathogenesis of myocardial fibrosis in CHF. Paeoniflorin (PF) is one of the main effective components of peony, which has been widely used in traditional Chinese medicine for its potent immunomodulatory and anti-inflammatory properties. However, the effects of PF on myocardial fibrosis remain unclear. <h3>Objective</h3> To exam whether PF protects myocardial fibrosis and improves cardiac function in isoprenaline-induced CHF rats. <h3>Methods</h3> Age matched male Wistar rats were used in this study. CHF and cardiac remodelling model was established by hypodermic injection of isoprenaline for ten days. After the CHF model establishment, the rats were randomly divided to receive placebo, PF (50 or 100 mg/kg/d, i.g.) or captopril for six weeks. Cardiac remodelling markers including ventricular mass, collagen volume fraction, perivascular collagen area and hydroxyproline concentration were studied. Echocardiography, Masson staining, immunohistochemistry, western blot and real-time PCR were performed. The protein and mRNA expression of PTEN (phosphatase and tensin homolog deleted on chromosome ten) were analysed. <h3>Results</h3> Compared to the untreated CHF rats, the perivascular collagen area, collagen volume fraction (30.97 ± 4.22% vs 13.75 ± 3.77%), hydroxyproline concentration (4.92 ± 0.78 μg/mg wet weight vs 2.08 ± 0.43 μg/mg wet weight), LVIDd (8.40 ± 0.52 mm vs 6.11 ± 0.58 mm) and LVIDs (6.44 ± 0.93 mm vs 4.49 ± 0.38 mm) were significantly lower in PF-treated (100 mg/kg/d) rats (p &lt; 0.05, n = 8). PF treatment also improved LVEF levels (46.44 ± 3.50% vs 60.89 ± 3.10%). Besides, the expressions of PTEN protein (0.11 ± 0.05 vs 0.63 ± 0.19, p &lt; 0.05) and mRNA (0.22 ± 0.06 vs 0.39 ± 0.02, p &lt; 0.01) were higher in PF-treated rats (n = 3). No damage of renal or liver function was detected in these rats (p &gt; 0.05). Furthermore, we also found that PF can accelerate myocardial fibroblast cell apoptosis and upregulate PTEN signalling <i><i>in vitro</i></i>. <h3>Conclusions</h3> Our findings indicate that PF could alleviate myocardial fibrosis and improve cardiac function in isoprenaline-induced CHF rats by upregulating PTEN signalling pathway. PF may be a potential therapeutic drug for CHF.