蝮蛇毒蛋白C激活物对大鼠心肌微血栓形成的抑制作用

Inhibitory effects of protein C activator from venom of agkistrodon halys rat with myocardial microthrombus

目的:观察蝮蛇毒蛋白C激活物(PCA)对大鼠心肌微血栓形成的影响,并进一步探讨其抗凝机制。方法:取健康雄性SD大鼠48只,随机分为假手术(SH)组、微血栓(MI)组、MI+PCA组和PCA组,其中MI+PCA组又分为1mg/kg、3mg/kg、6mg/kg三个剂量组,每组8只。以月桂酸钠复制大鼠心肌微血栓模型,测定并比较各组血浆中PAF、ET-1、vWF、MDA的含量及SOD的活性;心肌石蜡切片,常规HE染色,光镜观察;观察心肌梗死范围。结果:MI+PCA(3mg/kg)组及MI+PCA(6mg/kg)组大鼠血浆中PAF、ET-1、vWF、MDA的含量较MI组显著降低(P<0.05);病理亦显示MI+PCA(3mg/kg)组及MI+PCA(6mg/kg)组心肌无微血管血栓形成、无梗死;PCA组与SH组各指标无明显差异。结论:PCA可有效抑制微血栓形成,其除了可通过激活蛋白C系统抗凝外,保护血管内皮亦可能是其另一抗凝途径。

Objective ： To observe the effects of protein C activator from venom of agkistrodon halys on rats with myocardial microthrombus, with further investigation of the anticoagulant mechanisms. Mahods： 48 male SD rats were randomly divided into sham operation（SH）, microthrombus （MI）, protein C activator（PCA）and MI ＋ PCA group. MI ＋ PCA were subgrouped into 1 mg/kg, 3 mg/kg and 6 mg/kg administered group with 8 rats in each. The model of myocardial microthrombus was induced by soditan laumte for measuring and comparing the contents of vWF, PAF, ET-1, MDA and the activities of SOD in the plasma. The size of myocardial infarction was examined pathologically by using paraffin method, HE staining as well as microscopic observations. Results ： Compared with MI group, MI ＋ PCA in dose of 3 mg/kg or 6 m.g/kg group significantly reduced the contents of vWF＇, PAF, ET.1 and MDA in the plasma （ P 〈 0.05）, and no microthrombus and in- fraction were detected in group of MI ＋ PCA with a dose of 3 m.g/kg or 6 m.g/kg. The levels between SH and PCA group showed no significant difference. Conclusion ： PCA purified from venom of agkistrodon halys can evidently inhibit the formation of myocardial microthrombus by acti- vating protein C, also, the effect on protecting vaso-endothelia cells might be responsible for the anticoagulant effect.