五步蛇毒PCA改善脓毒症大鼠的血管低反应性

 目的:初步探讨五步蛇毒蛋白C激活剂（PCA）对脓毒症大鼠血管张力的影响。方法:SD雄性大鼠随机分成6组（n=6）：即假手术组（sham组）、模型组（LPS组）、PCA干预组（LPS+PCA组,分0.1 mg/kg、0.3 mg/kg和0.6 mg/kg剂量组）和阳性对照组（LPS+多粘菌素B组,0.2 mg/kg多粘菌素B）。采用离体血管灌流法,经生物信号处理系统测定主动脉环的张力变化。结果:LPS组大鼠的平均动脉血压（MABP）、心率（HR）、左室发展压（LVDP）、心室内压最大上升/下降速率（±dp/dtmax）均显著下降;PCA干预组各指标较LPS组均有明显改善。LPS组主动脉环对去氧肾上腺素（Phe）刺激的收缩反应和对乙酰胆碱（ACh）的舒张反应较sham组均下降;而PCA干预组（尤其是0.6 mg/kg剂量组）对Phe刺激的收缩反应和对ACh的舒张反应较LPS组则明显提高。LPS组的去内皮主动脉环对Phe刺激的收缩反应量效曲线较sham组明显下移,但PCA干预组的去内皮主动脉环对Phe刺激的收缩反应与LPS组相比无显著差异。各组主动脉环对硝普钠诱导的非内皮依赖性舒张反应差异无统计学意义。N-硝基-L-精氨酸甲酯和甲烯蓝预处理可以升高主动脉环对Phe的收缩反应。结论: 五步蛇毒PCA通过改善血管内皮功能而逆转脓毒症大鼠血管的低反应性,其机制可能与抑制NO-GC-cGMP通路的活化有关。

Improvement of vascular hyporesponsiveness in rats with sepsis by pro-tein C activator from Agkistrodon acutus venom

AIM:To investigate the effects of protein C activator (PCA) from Agkistrondon acutusvenom (AAV) on the tension of thoracic aorta rings isolated from the rats with sepsis. METHODS:The model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS). SD rats were randomly divided to 6 groups (n=6): sham group, LPS group, PCA intervention group (LPS+PCA, PCA at doses of 0.1 mg/kg, 0.3 mg/kg and 0.6 mg/kg) and LPS+ polymyxin B (at dose of 0.2 mg/kg) group. Using perfusion experiment in vitro, the tension of the aortic rings was measured by biological signal analytical system. RESULTS:The values of MABP, HR, LVDP and ±dp/dtmax were significantly lower in LPS group than those in sham group and LPS+PCA groups. Compared with sham group, the relaxation response to acetylcholine (ACh) and the contractile response of aorta rings induced by phenylephrine (Phe) were significantly decreased in LPS group, which were increased significantly in PCA intervention group (especially at dose of 0.6 mg/kg) compared with LPS group. The dose-response curve of aorta contraction with denuded endothelium induced by Phe shifted down significantly in LPS group compared with sham group, and no significant difference between LPS group and PCA intervention group was observed. Also no statistical difference was found in non-endothelium dependent relaxation of aortic rings induced by sodium nitroprusside among the groups. Pretreatment of N-nitro-L-arginine methl ester and methylene blue increased the contraction amplitude of aortic rings induced by Phe. CONCLUSION: PCA from AAV effectively reverses the hypoergia of the vessels in rats with sepsis through protecting vascular endothelium, the mechanism of which may be mediated by inhibiting NO-GC-cGMP signal transduction pathway.