高原环境导致静脉麻醉药敏感性增高的突触机制研究

In the plateau low oxygen environment, synaptic transmission of the central nervous system will be change,while its sensitivity increased significantly ,the effect of intravenous anesthetics can be increased at the same time,so the mechanism of this process deserves further study..Combined intravenous drug sensitivity and plateau environment,the rats lumbar spinal cord slice of colloidal layer neurons and mices brain slices of hippocampal CA1 area were choosed as our objects.We Observed normal areflexia and recovery time, as well as the oxygen partial pressure level in the plasma and cerebrospinal fluid of rats between each group of rats after given intravenous anesthetics;Recording spontaneous tiny postsynaptic currents, separation mEPSC,mIPSC and recording the frequency and the amplitude of the both two groups with using blind whole cell patch clamp;exploring whether calcium ion flow in participated in the presynaptic mechanism with the application of EDTA chelation of extracellular calcium solution perfusion,and by using permeability of the calcium ion chelating agent without calcium solution to explore whether the intracellular calcium release involved in its effect mechanism;Recording the current of receptor mediated and observing the low oxygen and propofol on its impact after given agonist..Expectations for providing theoretical basis for rational use of perioperative sedative drugs and reduce perioperative complications and mortality for patients with plateau.

在高原低氧环境下，中枢神经系统突触传递发生变化，敏感性显著升高，导致静脉麻醉药的作用也将增大，高原低氧环境对静脉麻醉药敏感性增高的突触机制值得进一步去研究。.将静脉麻醉药敏感性与高原环境相结合，以大鼠腰段脊髓片胶状质层神经元和小鼠的海马CA1区脑片作为研究对象。观察给予静脉麻醉药后各组大鼠反正反射消失和恢复的时间、大鼠血浆及脑脊液内的氧分压水平；采用盲法全细胞膜片钳记录自发性微小突触后电流、分离mEPSC和mIPSC并记录二者的频率和振幅；应用EDTA螯合的无钙溶液胞外灌流，探索钙离子内流是否参与了突触前机制，用可通透钙离子螯合剂的无钙溶液，探讨胞内钙离子释放是否参与了此影响机制；给予受体激动剂，记录受体介导的电流，并观察低氧和丙泊酚对此电流的影响。.期望为高原患者围手术期镇静药物的合理使用，减少围手术期并发症和死亡率提供理论依据。

高原环境的特点就是低氧低压，那么关于高原低压低氧麻醉药敏感性增高的机制研究就显得非常重要。低压低氧可能引起的中枢神经系统突触传递的改变，如促进兴奋性递质的释放、对抑制性突触传递的增强。将大鼠处于压力 10.1 kPa，氧浓度 10%的低压氧环境中，18 小时每天，处理 21 天，建立慢性低压低氧处理组；对照组-平原组在西安完成（西安，海拔 390m，大气氧分压 20kpa，同样处理 21 天），不管 mIPSC 的频率还是幅度，慢性低压低氧处理组大鼠（高原鼠）均显著高于平原组（对照组）（p<0.01），慢性低压低氧处理组大鼠抑制性突触传递显著强于平原鼠。将灌流液中加入0.5uM的TTX后，慢性低压低氧处理组大鼠脊髓SG区神经元mIPSC的频率和幅度均显著高于平原组（p<0.05），但是差异的幅度要小于两组大鼠CA1区神经元的mIPSC。先记录2min基线（baseline），然后给予丙泊酚（propofol，1uM），观察对mIPSC的影响。结果如图5所示，在平原组大鼠，1uM的丙泊酚仅能稍微增强CA1区神经元mIPSC的频率和幅度（20%左右）；但是在慢性低压低氧处理组大鼠，丙泊酚可以显著增强CA1区神经元mIPSC的频率和幅度（100%左右）。低压低氧处理对大鼠兴奋性突触传递活动的影响不大，主要是对抑制性突触传递活动的增强，从而介导了对丙泊酚等静脉麻醉药敏感性增加。