Original scientific paper
https://doi.org/10.3325/cmj.2015.56.439
A new Agkistrodon halys venom-purified protein C activator prevents myocardial fibrosis in diabetic rats
Shu Li
; Life Science College, Anhui Normal University, Wuhu, China
Yun Hong
; Department of Ultrasonography Yijishan Hospital, Wuhu, China
Xin Jin
; Department of Pharmacology Wannan Medical College, Wuhu, China
Genbao Zhang
; Department of Pathophysiology, Wannan Medical College, Wuhu, China
Zaichang Hu
; Department of Clinic Medicine, Wannan Medical College, Wuhu, China
Liuwang Nie
; Life Science College, Anhui Normal University, Wuhu, China
Abstract
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-β1) and interleukin 1 beta
(IL-1β) 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-β1 and IL-1β 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.
Keywords
Hrčak ID:
151737
URI
Publication date:
15.10.2015.
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