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目的 :探讨NO在失血性休克血管低反应性发生中的作用机制和防治。方法 :复制SD大鼠失血性休克模型 ,测定脊斜肌微动脉对去甲肾上腺素 (NE)的反应性。休克至血管反应性下降时 ,用同位素标记底物法测定脏器中NOS活性 ;分离肠系膜细动脉血管平滑肌细胞 (ASMC) ,用荧光探针和共聚焦显微镜测定NO底物左旋精氨酸 (L -Arg)和诱导性NOS(iNOS)抑制剂氨基胍 (AG)对膜电位的影响 ;回输全部失血同时给L -Arg和AG观察其对大鼠 2 4h存活率的影响。结果 :休克至血管反应性降低时 ,心、肝NOS活性增加。L -Arg对对照组大鼠ASMC的膜电位无影响 ,但可使反应性低下大鼠的ASMC超极化 ;用AG预处理ASMC ,则降低L -Arg引起的超极化幅度。回输全部失血时给AG可增加大鼠 2 4h存活率。结论 :HS后期ASMC中iNOS激活导致NO产生增加 ,并引起ASMC超极化可能是失血性休克后期血管低反应性发生的机制之一。
Objective: To investigate the mechanism and prevention and treatment of NO in the development of vascular hyporesponsiveness in hemorrhagic shock. Methods: The model of hemorrhagic shock in SD rats was duplicated and the reactivity of aortic branches to norepinephrine (NE) was measured. Shock to vasoreactivity decreased, NOS activity in organs was measured by isotope labeling substrate method; Mesenteric arteriole smooth muscle cells (ASMC) were isolated and measured by fluorescence probe and confocal microscopy. -Arg and iNOS inhibitor aminoguanidine (AG) on the membrane potential. All the blood was transfused and L-Arg and AG were simultaneously injected to observe the effect on the survival rate of rats at 24 h. Results: Nocardium and liver NOS activity increased from shock to decrease of vascular reactivity. L-Arg had no effect on the membrane potential of ASMCs in the control group, but hyperlodified the ASMCs in the hypoxic-responsive rats. Pretreatment with ASMC decreased the amplitude of L-Arg-induced hyperpolarization. Transfusion of all blood loss to AG can increase the rat 24 h survival rate. CONCLUSION: iNOS activation in late stage of HS leads to increased production of NO and the hyperpolarization of ASMC may be one of the mechanisms of post-hemorrhagic vascular hyporesponsiveness.