吡那地尔预处理提高失血性休克血管的反应性和钙敏感性

Pinacidil pretreatment increases vascular reactivity and calcium sensitivity after hemorrhagic shock

目的:观察吡那地尔预处理诱导对失血性休克血管反应性和钙敏感性的保护作用以及与蛋白激酶C(PKC)α、ε的关系。方法:观察不同剂量吡那地尔在休克前不同时间预处理,对失血性休克大鼠去甲肾上腺素(NE)的升压效应[平均动脉压(MAP)增幅]和收缩血管效应[肠系膜上动脉(SMA)管径变化]的影响,以及对SMA一级分支微血管环血管反应性和钙敏感性的影响;观察PKCα、PKCε抑制剂对吡那地尔预处理诱导保护效应的影响,以及吡那地尔预处理对PKCα、PKCε蛋白转位的影响,证实PKCα和PKCε的作用。结果:(1)失血性休克2 h后,NE的升压效应和收缩血管效应、SMA血管反应性和钙敏感性较正常组均显著降低(P<0.01),25μg/kgBW吡那地尔休克前30 min预处理可改善休克后的上述变化;(2)PKCα和PKCε的拮抗剂可以消除25μg/kg BW吡那地尔休克前30 min预处理诱导的失血性休克血管反应性和钙敏感性保护,使NE的Emax分别降低42.9%和62.9%(P<0.01),使Ca2+的Emax分别降低31.1%和56.1%(P<0.01);25μg/kg BW吡那地尔休克前30 min预处理使PKCα和PKCε的胞膜表达较休克2 h增高,胞浆表达较休克2 h降低(P<0.01)。结论:吡那地尔预处理可通过诱导PKCα和PKCε的转位和活化,提高大鼠失血性休克后血管的反应性和钙敏感性。

AIM： To observe the protective effects of protein kinase Cα（PKCα） and protein kinase Cε（PKCε） activated by pinacidil pretreatment on vascular reactivity and calcium sensitivity after hemorrhagic shock in rats.METHODS： The changes of the pressor effect（the change of mean arterial pressure） and vasoconstriction response（the changes of diameter） of superior mesenteric artery（SMA） to norepinephrine（NE） were observed.The vascular reactivity and calcium sensitivity of the first class arborization of SMA induced by pinacidil pretreatment with different volume and at different time points before shock were determined.The effects of PKCα and PKCε antagonists on the protection of pinacidil pretreatment,and the effects of pinacidil pretreatment on the translocation of PKCα and PKCε were also measured.RESULTS：（1） The pressor effect and vasoconstriction response of SMA to NE,and the vascular reactivity and calcium sensitivity of the first class arborization of SMA in 2 h shock group were significantly decreased as compared to those in normal controls（P0.01）.Pinacidil（25 μg/kg） pretreated at 30 min before shock attenuated the above changes.（2） The inhibitors of PKCα and PKCε suppressed the protective effects of pinacidil pretreatment（25 μg/kg pinacidil pretreated at 30 min before shock） on the vascular reactivity and calcium sensitivity.The Emax of NE was decreased by 42.9% and 62.9%,respectively（P0.01）.The Emax of Ca2＋ was decreased by 31.1% and 56.1%,respectively（P0.01）.Pinacidil（25 μg/kg） pretreated at 30 min before shock increased the protein expression of PKCα and PKCε on the membrane,and decreased the protein expression in the cytoplasm as compared to those in 2 h shock group（P0.01）.CONCLUSION： Pinacidil pretreatment activates PKCα and PKCε,and induces the increasing effects of vascular reactivity and calcium sensitivity after hemorrhagic shock in rats.