title: A new Agkistrodon halys venom-purified protein C activator prevents myocardial fibrosis in diabetic rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our results indicate that PCA has anti-fibrotic effects and that it may be used to treat myocardial fibrosis.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Hong
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Genbao
authors.initials: G
authors.lastname: Zhang
authors.forename: Zaichang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Liuwang Nie, The Provincial Key Lab of the Conservation and Exploitation Research of Biological Resources in Anhui Life Science College, Anhui Normal University, Beijing East Road 1#, Wuhu 241000, People's Republic of China, lwnie@ahnu.edu.cn.
authors.forename: Liuwang
authors.initials: L
authors.lastname: Nie
mesh_terms: D017836:Agkistrodon; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D056148:Chromatography, Reverse-Phase; D003094:Collagen / Q000378:metabolism; D003435:Crotalid Venoms / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004719:Endomyocardial Fibrosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D006352:Heart Ventricles / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology; D009842:Oligopeptides / Q000302:isolation & purification / Q000494:pharmacology*; D011486:Protein C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000097:blood
chemical_list: D001786:Blood Glucose; D003435:Crotalid Venoms; D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D009842:Oligopeptides; D011486:Protein C; D053773:Transforming Growth Factor beta1; C047135:protein C activator peptide; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D008687:Metformin; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat