血管平滑肌L型钙通道抑制参与重症休克血管低反应性的发生
发布时间：2018-11-24 18:36
【摘要】：休克是一个复杂的病理过程，根据其严重程度分为可逆性休克和不可逆性休克(重症难治性休克)。重症休克的发生是众多创伤及感染性疾病发展的共同归宿，是导致病人死亡率居高不下的直接原由。当进入重症难治性阶段，微血管对升压药物反应性丧失致使休克病人出现顽固性低血压，并对所有的治疗措施均处于无反应状态。因此，解决微血管的低反应性问题是治愈休克的关键。 近期的实验证明，失血性休克2小时后，血管平滑肌钾通道(BK_(Ca)和K_(ATP))大量开放，电流增加，细胞内钙依赖性发生变化，导致细动脉平滑肌细胞(arteriolar smooth muscle cells，ASMC)发生超极化。钙通道、钙释放通道、钠通道的抑制，钾通道活动的增强均可导致细胞膜超极化。其中，L型钙通道(L-type calcium channels，L-Ca)调节大部分可兴奋性和非兴奋性细胞的活动，是细胞膜外钙离子的内流的主要途径。本室的工作证明，休克时ASMCs超极化。给予升压药物(NE)刺激后，细胞内钙离子浓度升高仅为正常时的50％，而且主要是外钙的内流受到抑制。所以我们推测在休克后期，，细胞膜的超极化抑制了ASMCs上的L-Ca通道，但没有直接测定过此通道的变化。本课题采用膜片钳与荧光探针技术研究休克后期平滑肌细胞L-Ca的变化及其与血管平滑肌反应性下降的关系，用实验证明以上推测，为休克的临床治疗提供进一步的理论依据。
[Abstract]:Shock is a complicated pathological process, which can be divided into reversible shock and irreversible shock according to its severity. The occurrence of severe shock is the common destination for the development of many trauma and infectious diseases and the direct cause of high mortality. When the severe refractory phase was reached, the loss of microvascular reactivity to pressor drugs caused intractable hypotension in shock patients, and no response to all treatment measures was observed. Therefore, to solve the problem of microvascular hyporesponsiveness is the key to cure shock. Recent experiments have shown that after hemorrhagic shock for 2 hours, the potassium channels (BK_ (Ca) and K _ (ATP) of vascular smooth muscle were opened, the current increased, and the intracellular calcium dependence changed, which resulted in (arteriolar smooth muscle cells, of arteriolar smooth muscle cells. ASMC) hyperpolarization. The inhibition of calcium channel, calcium release channel, sodium channel and enhancement of potassium channel activity can lead to cell membrane hyperpolarization. L-type calcium channel (L-type calcium channels,L-Ca) regulates the activity of most excitable and non-excitatory cells and is the main pathway of extracellular calcium influx. Our work proves that ASMCs hyperpolarization occurs during shock. After (NE) stimulation, the increase of intracellular calcium concentration was only 50% of the normal level, and the inward flow of extracellular calcium was inhibited. So we speculated that in the late stage of shock, the hyperpolarization of cell membrane inhibited the L-Ca channel on ASMCs, but we did not measure the change of this channel directly. In this study, patch clamp and fluorescence probe technique were used to study the changes of L-Ca in smooth muscle cells and its relationship with vascular smooth muscle reactivity in the late stage of shock. To provide further theoretical basis for the clinical treatment of shock.
【学位授予单位】：第一军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363
本文编号：2354608
[Abstract]:Shock is a complicated pathological process, which can be divided into reversible shock and irreversible shock according to its severity. The occurrence of severe shock is the common destination for the development of many trauma and infectious diseases and the direct cause of high mortality. When the severe refractory phase was reached, the loss of microvascular reactivity to pressor drugs caused intractable hypotension in shock patients, and no response to all treatment measures was observed. Therefore, to solve the problem of microvascular hyporesponsiveness is the key to cure shock. Recent experiments have shown that after hemorrhagic shock for 2 hours, the potassium channels (BK_ (Ca) and K _ (ATP) of vascular smooth muscle were opened, the current increased, and the intracellular calcium dependence changed, which resulted in (arteriolar smooth muscle cells, of arteriolar smooth muscle cells. ASMC) hyperpolarization. The inhibition of calcium channel, calcium release channel, sodium channel and enhancement of potassium channel activity can lead to cell membrane hyperpolarization. L-type calcium channel (L-type calcium channels,L-Ca) regulates the activity of most excitable and non-excitatory cells and is the main pathway of extracellular calcium influx. Our work proves that ASMCs hyperpolarization occurs during shock. After (NE) stimulation, the increase of intracellular calcium concentration was only 50% of the normal level, and the inward flow of extracellular calcium was inhibited. So we speculated that in the late stage of shock, the hyperpolarization of cell membrane inhibited the L-Ca channel on ASMCs, but we did not measure the change of this channel directly. In this study, patch clamp and fluorescence probe technique were used to study the changes of L-Ca in smooth muscle cells and its relationship with vascular smooth muscle reactivity in the late stage of shock. To provide further theoretical basis for the clinical treatment of shock.
【学位授予单位】：第一军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363
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相关期刊论文 前4条
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本文编号：2354608
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