缺血预适应诱导的失血性休克血管反应性和钙敏感性保护

Protective effect of ischemia preconditioning on vascular reactivity and calcium sensitivity in rats after hemorrhagic shock

目的观察缺血预适应诱导失血性休克血管反应性和钙敏感性保护。方法采用112只清洁级Wistar大鼠,雌雄各半,体质量220～230g,观察不同失血量(2.5%、5%、10%血容量)、在休克前不同时间(0.5、1、2、3h)缺血预适应,对休克血管反应性和钙敏感性的保护、蛋白激酶Cα(protein kinase Cα,PKCα)和蛋白激酶Cε(protein kinase Cε,PKCε)抑制剂对其保护效应的影响、缺血预适应肠系膜上动脉(superior mesenteric artery,SMA)中PKCα、PKCε的转位。结果①5%血容量休克前0.5h缺血预处理可减轻休克后降低的去甲肾上腺素(norepinephrine,NE)升压效应和收缩血管效应、SMA血管反应性和钙敏感性,使其分别增高25.5%、25.0%、42.3%和40.9%(P<0.01);②PKCα和PKCε拮抗剂可消除缺血预适应诱导的血管反应性保护(分别降低45.0%和72.4%,P<0.01)和钙敏感性保护(分别降低59.0%和52.5%,P<0.01);缺血预适应可促进PKCα和PKCε的转位(P<0.01)。结论缺血预适应通过活化PKCα和PKCε诱导失血性休克后血管反应性和钙敏感性的保护。

Objective To observe the protection against ischemia preconditioning-induced vascular reactivity and calcium sensitivity after hemorrhagic shock. Methods Effects of protein kinase Cα （PKCα） and protein kinase Cε（PKCε） antagonists on ischemia preconditioning-induced vascular reactivity and calcium sensitivity were observed in rat model after different volumes of blood loss （2.5%,5% and 10%） at different time points （0.5,1,2 and 3 h） before shock. Effects of ischemia preconditioning on translocation of PKCα and ε in superior mesenteric artery （SMA） were also observed. Results Ischemia preconditioning with 5% blood volume 30 min before shock improved the decreased blood pressure elevation and vasoconstriction responses to norepinephrine （NE）,and the vascular reactivity and calcium sensitivity were decreased 2 h after shock by 25.5%,25.0%,42.3% and 40.9% respectively （P0.01）. The inhibitor of PKCα and ε suppressed the protective effects of ischemia preconditioning on vascular reactivity by 45.0% and 72.4% respectively （P0.01） and calcium sensitivity by 59.0% and 52.5% respectively （P0.01）. Ischemia preconditioning promoted the translocation of PKCα and PKCε from cytoplasm to membrane （P0.01）. Conclusion Ischemia preconditioning can protect vascular reactivity and calcium sensitivity after hemorrhagic shock in rats through PKCα and PKCε.