徐竞 刘良明

    【摘要】 目的 观察血管平滑肌钙失敏在大鼠失血性休克(HS)血管低反应性中的作用。方法 取失血性休克大鼠肠系膜上动脉(SMA)，利用离体血管环张力测定技术，以血管环对梯度浓度去甲肾上腺素(NE)的收缩力反映血管反应性，用去极化状态下(120 mmol/L K+)血管环对梯度浓度Ca2+的收缩力反映血管的钙敏感性，观察失血性休克低反应血管是否存在钙敏感性降低以及钙敏感性调节剂血管紧张素Ⅱ(AngⅡ)、胰岛素以及Rho-激酶特异性抑制剂Fasudil是否可以通过调节钙敏感性来调节血管反应性。结果失血性休克后SMA对NE的反应性和钙敏感性均显著下降，表现为NE的量-效曲线明显右移，NE的最大收缩力(Emax)和-lg(EC 50)(pD 2)降低(P<0.05或P<0.01)；Ca2+的量-效曲线明显右移，Ca2+的Emax和pD 2降低(P<0.05或P<0.01)。具有钙敏感性增强作用的AngⅡ(10-9 mol/L)可使NE和Ca2+的量-效曲线左移，使NE和Ca2+的Emax增高(P<0.05或P<0.01)，而具有钙敏感性抑制作用的胰岛素(100 nmol/L)可使NE和Ca2+的量-效曲线右移，NE和Ca2+的Emax降低(P<0.05或P<0.01)，Fasudil预处理可消除AngⅡ对NE诱导的血管收缩反应的增强效果，降低钙敏感性。结论失血性休克血管平滑肌细胞存在钙敏感性降低，血管平滑肌细胞钙敏感性降低在失血性休克血管低反应性的发生中起重要作用。

    【关键词】 休克，失血性； 血管低反应性； 钙敏感性； 钙失敏

    Role of calcium desensitization in vascular hyporeactivity in hemorrhagic shock

    XU Jing, LIU Liang-ming.

    State Key Laboratory of Trauma, Burns and Combined Injury, The Second Department of Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042, China

    【Abstract】 Objective To evaluate the role of calcium desensitization of vascular smooth muscle in vascular hyporeactivity following hemorrhagic shock (HS) in rats. Methods The superior mesenteric artery(SMA) from HS model of rat was adopted to assay the vascular reactivity and calcium sensitivity by observing its contractibility initiated by norepinephrine(NE) and Ca2+under depolarizing conditions(120 mmol/L K+) with the aid of an isolated organ perfusion system. The experiment was conducted in two parts. In the first part, calcium desensitization was present whether or not in the response-decreased blood vessels was observed, and in the second part, whether angiotensinⅡ (AngII) and insulin which were calcium sensitivity regulating agents, and a relatively selective inhibitor of Rho-kinase, Fasudil, could regulate the vascular reactivity through regulating the calcium sensitivity was tested. Results As compared with the normal group, the cumulative dose-response curve of SMA to NE and Ca2+in shock group was shifted to the right, the maximal contraction (Emax) and -lg(EC 50)(pD 2) of NE and Ca2+ were decreased significantly(P<0.05 or P<0.01). AngII shift the cumulative dose-response curve of NE and Ca2+to the left, and increased the contractile response of NE and Ca2+(P<0.05 or P<0.01). On the contrary, insulin rendered the cumulative dose-response curve of NE and Ca2+shift to the right and decreased the contractile response of NE and Ca2+(P<0.05 or P<0.01). Pretreatment with Fasudil abolished the enhancing effect of AngII on vascular contraction produced by NE, and reduced the calcium sensitivity. Conclusion Calcium desensitization is a physiological condition which exists in the vascular smooth muscle of HS rat, and it plays an important role in vascular hyporeactivity, which is one of the important mechanism of the abnormal condition of vascular hyporeactivity. ......