蛋白激酶C和蛋白激酶G对失血性休克大鼠血管平滑肌细胞钙敏感性的调节作用  

Regulatory effect of protein kinase C and protein kinase G on calcium sensitivity of vascular smooth muscle cells following hemorrhagic shock

作　　者：李涛[1] 刘良明[1] 刘建仓[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所二室,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》2007年第5期257-260,共4页Chinese Critical Care Medicine

基　　金：国家自然科学基金资助项目（30370563,30600228,30625037）;国家“973”计划资助项目（2005CB522601）

摘　　要：目的探讨蛋白激酶C（PKC）、蛋白激酶G（PKG）对失血性休克大鼠血管平滑肌细胞钙敏感性的调节作用。方法经股动脉放血使平均动脉压维持在40mmHg（1mmHg-0．133kPa）2h制备失血性休克大鼠模型。采用离体血管环张力测定技术，测定在失血性休克大鼠肠系膜上动脉（SMA）血管环去极化状态下（120mmol／L K^＋）对梯度浓度Ca^2＋的收缩反应性（钙敏感性）变化；同时观察PKC、PKG活性调节剂对钙敏感性的影响。测定大鼠SMA的PKC、PKG活性变化，分析PKC、PKG活性变化与血管钙敏感性变化间的关系。结果休克2h SMA血管环对钙敏感性明显降低，其量-效曲线明显右移，最大收缩力（Emax）明显降低（P均〈0．01）。PKC激动剂PMA1×10^-7mol／L可明显提高休克血管环对钙敏感性，PKC拮抗剂staurosporine 1×10^-7mol／L可降低休克血管环对钙敏感性（P〈0．05或P〈0．01）；PKG激动剂8Br—cGMP1×10^-1mol／L可使休克血管钙敏感性降低，其拮抗剂KT-58231×10^-1mol／L可提高休克血管钙敏感性（P均〈0．05）。休克2hSMA的PKC活性明显降低，PKG活性明显升高（P〈0．05和P〈0．01），分别与休克血管钙敏感性变化呈正相关和负相关（P均〈0．01）。结论PKC和PKG参与了失血性休克血管平滑肌细胞钙敏感性的调控，PKC可上调血管平滑肌细胞的钙敏感性，PKG可下调其钙敏感性。Objective To observe the effect of protein kinase C （PKC） and protein kinase G （PKG） on calcium desensitization following hemorrhagic shock in rats. Methods The model of hemorrhagic shock was replicated by blood letting and maintaining mean arterial pressure at 40 mm Hg （1 mm Hg：0. 133 kPa） for 2 hours. The superior mesenteric artery （SMA） in hemorrhagic shock rats was adopted to assay the calcium sensitivity via observing the contraction initiated by calcium under depolarizing conditions （120 mmol/L K^＋） with isolated organ perfusion system. Meanwhile, the effects of the PMA （PKC agonist）, staurosporine （PKC inhibitor）, 8Br- cGMP （PKG agonist） and KT- 5823 （PKG inhibitor） on calcium sensitivity and the changes in PKC and PKG activities in SMA were observed following hemorrhagic shock. Results The calcium sensitivity of SMA following hemorrhagic shock was significantly decreased, and the dose -effect curve shifted to the right significantly, maximum energy （Emax） decreased significantly at 2 hours following shock （all P〈0.01）. The PMA （1× 10^- 7 mol/L） and KT - 5823 （1× 10^- 6 mol/L） significantly increased hemorrhagic shock - induced decrease in calcium sensitivity （P 〈0.05 or P 〈 0. 01）. Staurosporine （1× 10^-7 mol/L） and 8Br - cGMP （1× 10^-4 mol/L） further decreased calcium sensitivity after shock （P〈0.05 or P〈0.01）. The activity of PKC was decreased and PKG activity was increased 2 hours following shock （P〈0.05 and P 〈 0.01）, and was positively and negatively correlated with calcium sensitivity of SMA, respectively （both P〈0.01）. Conclusion PKC and PKG take part in the regulation of calcium sensitivity following hemorrhagic shock. PKC up - regulates calcium sensitivity! and PKG down - regulates calcium sensitivity in vascular smooth muscle cells following hemorrhagic shock.

关 键 词：血管反应性 钙敏感性 休克 失血性 蛋白激酶 

分 类 号：R686[医药卫生—骨科学]