摘要
目的:观察失血性休克后,Zipper相互作用蛋白激酶(ZIPK)在蛋白激酶Cα(PKCα)、蛋白激酶Cε(PKCε)调节失血性休克大鼠血管钙敏感性中的作用。方法:采用离体微血管环张力测定技术,观察褪膜后抑制ZIPK对PKCα、PKCε激动剂增高失血性休克肠系膜上动脉(SMA)一级分支微血管钙敏感性作用的影响;同时观察缺氧血管平滑肌细胞(VSMCs)在PKCα、PKCε激动剂作用下ZIPK蛋白表达、活性的变化。结果:(1)失血性休克后SMA钙敏感性明显降低,PKCα、PKCε激动剂可显著增高休克后的SMA钙敏感性,使Ca2+的Emax由正常对照的47.2%分别增高至66.5%(P<0.01)和66.3%(P<0.01);抑制ZIPK,可显著降低PKCα激动剂和PKCε激动剂的增高休克SMA钙敏感性的作用,Ca2+的Emax降低至正常对照组的42.6%(P<0.01)和47.5%(P<0.01)。(2)缺氧2 h的VSMCs中,ZIPK蛋白表达降低,活性降低,PKCα、PKCε激动剂可增高缺氧VSMCs的ZIPK蛋白表达和活性。结论:PKCα、PKCε可能通过改变ZIPK的蛋白表达和活性,来调节失血性休克后血管的钙敏感性。
AIM： To observe the role of zipper- interacting protein kinase （ZIPK） in the regulatory effects of protein kinase Cα （PKCα） and protein kinase Cε （PKCε） on calcium sensitivity during hemorrhagic shock （HS） in rats. METHODS ： The skinned first class arborization of superior mesenteric artery （SMA） from HS rats were adopted to observe the influence of inhibitor of ZIPK on the effects of PKCα and PKCε agonists on calcium sensitivity after shock via measuring the contraction initiated by Ca2＋ with isolated organ perfusion system, hypoxic vascualr smooth muscle cells （VSMCs） were adopted to measure the protein expression and activity of ZIPK after applying PKCα and PKCε agonists following hypoxia via Western blotting. RESULTS ： （ 1 ） The calcium sensitivity of SMA was decreased after 2 h shock, and increased by agonists of PKCα and PKCε. Emax of Ca2 ＋ was increased from 47.2% to 66.5% （P 〈 0. 01 ） and 66.3% （ P 〈 0.01 ） of normal control respectively as compared with 2 h shock group. The increasing effects of PKCOt and PKCα agonists on calcium sensitivity of SMA after 2 h shock were weakened by the inhibitor of ZIPK. The cumulative dose - response curve of Ca2＋ was shifted to the right, the Emax of Ca2＋ was decreased to 42.6% and 47.5% of normal control （P 〈 0.01 ） , respectively. （2） The protein expression and activity of ZIPK in VSMCs were decreased after 2 h hypoxia, and were increased by the agonists of PKCα and PKCε following 2 h hypoxia. CONCLUSION： PKCα and PKCε regulate the calcium sensitization probably through changing the protein expression and activity of ZIPK following HS in rats.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2009年第6期1041-1045,共5页
Chinese Journal of Pathophysiology
基金
国家重大基础研究计划973资助项目(No.2005CB522601)
国家杰出青年科学基金资助项目(No.30625037)
