山羊复合麻醉中枢作用机制的研究

Based on the combined anaesthetic for goat developed by our laboratory，the combined anaesthetic and its components xylazine, qiangtongning, droperidol were injected into muscle of goat respectively, then the cerebral cortex, cerebellum, deutocerebrum, cerebral ganglion and cornu ammonis were collected during cornu ammonis, intermediate stage, later period of anesthesia, and initial stage of palinesthesia, later stage of palinesthesia. The effects of each components and combined anaesthetic on center signal transduction system, neurotransmitter and synaptosome calcium dynamics, and expression of c-fos and c-jun of intra-cellular, dynamics of calcium for nerve cell were studied. To interpret the relationship among those three component elements and effect of junk on above system. Then identify the effects mechanisms, site of action of every components of combined anaesthetic for goat. To analyze if there existed superimposing area, supplementary overlap for dead zone, cooperativeness of action mechanism among every components. Eventually find the evidence to modified combination of anaesthetic, and establish foundation for research of other combined anaesthetic of ruminant.

课题以前期研制的山羊复合麻醉剂为基础，将复合制剂中隆朋、强痛宁、氟哌利多及复合制剂分别对山羊肌注给药，于注射后诱导期、麻醉中期、麻醉后期、苏醒初期、苏醒后期5个时间点分别取大脑皮层、小脑、中脑、丘脑及海马等脑区，研究单剂及复合制剂对山羊中枢信号转导系统、神经递质与突触体钙动力学、胞内c-fos和c-jun基因表达与神经细胞钙动力学的影响，阐明麻醉药物对其影响及这三大环节之间的相互关系，明确山羊复合麻醉剂组方中每一种药物的中枢作用机制、作用部位，分析单剂之间是否具有叠加区域、盲区补充覆盖及作用机制的协同性。找出对组方改进的依据，同时也为下一步其他反刍动物复合麻醉的研究奠定基础。

本项目成功研究出山羊复合麻醉药组方，研究结果表明麻醉药物对抑制性神经递质作用部位为小脑、海马、丘脑，赛拉嗪和咪达唑仑表现为协同作用; 噻啦嗪、咪达唑仑及复合麻醉制剂对细胞膜泵功能、AC-cAMP-PDE信号转导系统及对神经细胞和突触体钙动力学及钙通道亚型呈现抑制作用，通过该机制发挥麻醉调控作用；通过对奋性氨基酸神经递质产生抑制作用，对抑制性神经递质产生促进作用而实现麻醉作用，其启动是通过引起大脑皮质、丘脑、海马、小脑不同时间点c-fos mRNA和c-jun mRNA表达增加实现麻醉药物镇痛作用。药物药代动力学与临床效果及中枢机制的研究，阐明麻醉药物作用与时效的关系，证明本研究组方的科学性和临床应用的合理性。研究结果从中枢水平明确麻醉机制，为今后麻醉相关研究奠定基础，为麻醉机制研究开辟新的思路。