A new Agkistrodon halys venom-purified protein C activator prevents myocardial fibrosis in diabetic rats

Aim To assess the effects of protein C activator (PCA) from Agkistrodon halys snake venom on cardiac fibrosis in streptozotocin (STZ) induced diabetic rat model, and investigate the mechanisms of its action. Methods PCA was identified by one-dimensional reversed phase liquid chromatography - mass spectrometry/mass spectrometry. Male Sprague-Dawley rats (120-140 g) were randomly assigned to negative control (NC) and diabetic group. Diabetes was induced by STZ in high-fat diet fed rats. Diabetic group was subdivided into three groups: diabetic group (DM), diabetic group treated with PCA (0.5, 2, and 8 mg/kg), and diabetic group treated with metformin (5 mg/kg, positive control). NC and DM groups received the same volume of distilled water. Left ventricular mass index (LVWI) and collagen volume fraction were measured by hematoxylin and eosin and Masson staining. Transforming growth factor beta-1 (TGF-beta 1) and interleukin 1 beta (IL-1 alpha) levels were determined by enzyme-linked immunosorbent assay. Results The diabetic rat model was successfully established by STZ induction and high-fat diet. Glucose level, LVWI, TGF-beta 1 and IL-1 beta level, and collagen volume fraction were significantly reduced in diabetic rats treated by PCA in a dose-dependent manner (P < 0.050), especially in the high dose (8 mg/kg) group (P < 0.010), compared to diabetes group. The high dose PCA had the same effect as metformin positive control in reducing the level of fasting blood glucose. PCA decreased the expression of MMP-2 and reduced that of TIMP-2. Conclusion Our results indicate that PCA has anti-fibrotic effects and that it may be used to treat myocardial fibrosis.