精氨酸血管加压素恢复失血性休克大鼠血管反应性和钙敏感性与蛋白激酶C亚型的关系  

Effect of arginine vasopressin on vascular reactivity and calcium sensitivity of vascular smooth muscle and its relationship to protein kinase C following hemorrhagic shock in rats

作　　者：杨光明[1] 李涛[1] 徐竞[1] 明佳[1] 刘良明[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所第二研究室创伤烧伤与复合伤国家重点实验室,重庆400042

出　　处：《中国危重病急救医学》2008年第3期139-143,共5页Chinese Critical Care Medicine

基　　金：基金项目：国家自然科学基金资助项目（30625037）;国家重点基础研究发展计划（973）资助项目（2005CB522601）

摘　　要：目的探讨精氨酸血管加压素（AVP）对失血性休克大鼠血管反应性和钙敏感性的恢复作用与蛋白激酶C（PKC）亚型的关系。方法取失血性休克大鼠肠系膜上动脉（SMA）并去除内皮，利用离体血管环张力测定技术，观察了AVP（5×10^-11、5×10^-10和5×10^-9mol／L）调节对休克SMA对去甲肾上腺素（NE）反应性和钙敏感性的作用及其与PKCα、δ亚型的关系。结果AVP（5×10^-11、5×10^-10和5×10^-9mol／L）可明显恢复休克后的血管反应性和钙敏感性，使SMA对NE和Ca^2＋的量-效曲线明显左移，血管环产生的最大收缩张力（Emax）升高（P均〈0.01），且呈一定的剂量依赖关系，各剂量组间比较差异均有统计学意义（P均〈0.05）。而特异性的PKCα、δ亚型抑制剂Gǒ6976（5×10^-6mol／L）和Rottlerin（10^-5mol／L）均可拮抗AVP（5×10^-10mol／L）诱导的休克后血管反应性和钙敏感性升高，抵消了AVP诱导的NE和Ca^2＋的量-效曲线左移，使NE的Emax明显降低（P〈0.05或P〈0．01）。结论AVP能剂量依赖性地升高失血性休克大鼠的血管反应性和血管平滑肌钙敏感性，其机制可能与PKCα、δ亚型激活有关。Objective To investigate the effect of arginine vasopressin （AVP） on vascular reactivity and calcium sensitivity following hemorrhagic shock and their relationship to protein kinase C （PKC） isoforms. Methods With endothelium denuded superior mesenteric artery （SMA） rings procured from rats in hemorrhagic shock, the effects of AVP （5×10^-11、5×10^-10 and 5×10^-9mol/L） on contractile responses to norepinephrine （NE） and calcium sensitivity of SMA from hemorrhagic shock in rats and their relationship to α and δ isoforms of PKC with isolated organ perfusion system were observed. Results AVP （5×10^-11, 5×10^-10 and 5×10^-9mol/L） markedly restored the vascular reactivity and calcium sensitivity following hemorrhagic shock, converting the cumulative concentration-response curve of NE and Ca^2＋ shift to the left, and its maximum concentration force （Emax） was significantly increased （all P〈0.01） in a concentration dependent manner. Significant statistical differences were observed between the AVP groups （all P〈0.05）. Gǒ6976（ 5×10^-6 mol/L） and Rottlerin （10^-5 mol/L）,respectively as the specific PKCα and PKCδ isoforms inhibitor, antagonized AVP （ 5×10^-10 mol/L）-induced increase in vascular reactivity and calcium sensitivity of SMA following hemorrhagic shock and inhibited AVP-induced shift to the left of cumulative concentration-response curve of NE and Ca^2＋, and the Emax was significantly decreased （P〈0.05 or P〈0.01）. Conclusion AVP significantly restored the decreased vascular reactivity and calcium sensitivity of vascular smooth muscle following hemorrhagic shock, and its underlying mechanisms may be related to both α and δ isoforms of PKC activation.

关 键 词：失血性休克 精氨酸血管加压素 蛋白激酶 血管反应性 钙敏感性 

分 类 号：R459.7[医药卫生—急诊医学]