右美托咪定预处理剂量依赖性改善罗哌卡因致惊厥及惊厥后负性情绪

发布时间：2018-05-22 09:24

本文选题：右美托咪定 + 罗哌卡因　；参考：《第四军医大学》2015年硕士论文

【摘要】：研究背景:需要手术治疗的患者常常处于强烈的应激环境之中,因局麻药导致的不良反应的发生会加剧患者的精神压力,对患者的康复极为不利,甚至会危及生命安全。罗哌卡因是一种新型的酰胺类局部麻醉药,它较其他同类局麻药更为安全,而且毒副反应少,但因其过量使用或误入血管而造成的因血药浓度过高而出现的不良反应也屡见不鲜。局麻药所导致的中枢神经系统毒性,在临床上最为常见的并发症如惊厥,严重者甚至可以危及生命,而惊厥控制后的患者也常常表现出焦虑、抑郁等负性情绪,这些都直接影响患者预后和医疗体验。那么,临床上有没有一种药物既能有效地预防惊厥的发生又能合理的改善不良反应造成的负性情绪呢?咪达唑仑是目前用于控制和预防局麻药致惊厥的经典药物,但反复、大剂量的静脉内用药所致的呼吸抑制是其严重致死性不良反应。右美托咪定是一种新型的高选择性α2-肾上腺素受体激动剂,能产生满意的镇静及镇痛效果,而且对自主呼吸无明显的影响,目前已广泛应用于围术期镇静、镇痛和脏器保护的临床实践。但右美托咪定预处理是否能有效预防局麻药导致的惊厥,且其能否改善惊厥后的负性情绪及其作用机理都是亟待我们解决的问题。实验目的:本实验拟观察剂量梯度右美托咪定预处理对罗哌卡因致惊厥及惊厥后负性情绪的影响,探讨右美托咪定对基底外侧杏仁核与中央杏仁核p-ERK表达的影响在罗哌卡因致惊厥及惊厥后负性情绪中的作用。方法:本实验第一部分拟采用行为药理学的方法,通过离线视屏记录评估小鼠惊厥行为,探讨不同剂量右美托咪定预处理对罗哌卡因致惊厥的半数致惊厥剂量的影响。第二部分拟综合采用行为药理学、免疫组织化学和分子生物学的方法探讨不同剂量右美托咪定预处理对各半数致惊厥剂量罗哌卡因诱导的惊厥及惊厥后小鼠的负性情绪的影响,及其在惊厥后2 h基底外侧杏仁核和惊厥后24 h时中央杏仁核内p-ERK表达的影响。结果:本实验结果表明:2.4、4.8和9.6μg/kg右美托咪定预处理可剂量依赖性地(1)增加21.72%、25.70%和41.98%罗哌卡因的半数致惊厥剂量;(2)延长半数致惊厥剂量罗哌卡因致惊厥的惊厥潜伏期,并缩短惊厥持续时间;(3)增加旷场试验中小鼠中央区域活动时间百分比和高架十字迷宫试验中开臂停留时间百分比及开臂进入次数百分比,提示其呈可剂量依赖性改善惊厥后的焦虑/抑郁样负性情绪;(4)抑制惊厥后2 h时基底外侧杏仁核及惊厥后24 h时中央杏仁核内p-ERK的过表达。结论:基于以上实验结果,我们认为右美托咪定预处理可剂量依赖性地改善罗哌卡因致惊厥的发生及惊厥后的负性情绪,该保护作用可能分别与其抑制基底外侧杏仁核和中央杏仁核内p-ERK的过表达有关。
[Abstract]:Background: patients in need of surgical treatment are often in a strong stress environment, the occurrence of adverse reactions caused by local anesthetic drugs will aggravate the mental stress of patients, will be extremely adverse to the recovery of patients, and even endanger the safety of life. Ropivacaine is a new type of local anesthetic, which is safer than other local anesthetics and has fewer side effects. However, the adverse reactions caused by excessive use or misuse of blood vessels due to high blood concentration are common. The central nervous system toxicity caused by local anesthetic drugs, the most common clinical complications such as convulsion, severe or even life-threatening, and convulsion control patients also often show anxiety, depression and other negative emotions, These all directly affect the prognosis and medical experience of patients. So, is there a drug that can effectively prevent convulsions and reasonably improve the negative mood caused by adverse reactions? Midazolam is a classical drug used to control and prevent convulsions caused by local anesthetics at present, but repeated respiratory inhibition caused by large doses of intravenously administered drugs is a serious fatal adverse reaction. Desmetomidine is a new type of highly selective 伪 2-adrenoceptor agonist, which can produce satisfactory sedative and analgesic effects, and has no obvious effect on spontaneous respiration. It has been widely used in perioperative sedation. Clinical practice of analgesia and organ protection. However, whether dexmetomidine pretreatment can effectively prevent seizures caused by local anesthetics, and whether it can improve the negative emotion after convulsion and its mechanism of action are urgent problems to be solved. Objective: to observe the effect of dose gradient dexmetomidine preconditioning on convulsion induced by ropivacaine and negative emotion after convulsion. To investigate the effect of dexmetomidine on the expression of p-ERK in basal lateral amygdaloid nucleus and central amygdala in ropivacaine induced convulsion and postconvulsive negative emotion. Methods: in the first part of the experiment, behavioral pharmacology was used to evaluate the convulsion behavior of mice by off-line video recording, and to explore the effect of dexmetomidine preconditioning on the half convulsion dose of ropivacaine induced convulsion. In the second part, we used behavioral pharmacology, immunohistochemistry and molecular biology to investigate the effects of dexmetomidine preconditioning on convulsion induced by ropivacaine and negative emotion in mice after convulsion. The expression of p-ERK in the basolateral amygdala at 2 h after convulsion and in the central amygdala at 24 h after convulsion. Results: the results showed that preconditioning with 2. 4 渭 g/kg and 9. 6 渭 g/kg dexmetomidine could increase the convulsion latency of ropivacaine by 21.72% 25.70% and 41.98% in a dose-dependent manner. The mean duration of convulsion was shortened. The percentage of activity time in the central area of mice in open field test, the percentage of open arm retention time and the percentage of entry times of open arm in elevated cross maze test were increased. It suggested that it could improve the anxiety / depression-like negative emotion in a dose-dependent manner) and inhibit the overexpression of p-ERK in the basolateral amygdala at 2 h after convulsion and in the central amygdala at 24 h after convulsion. Conclusion: based on the above results, we believe that dexmetomidine pretreatment can improve the occurrence of convulsion induced by ropivacaine and the negative emotion after convulsion in a dose-dependent manner. The protective effect may be related to the inhibition of p-ERK overexpression in basolateral amygdala and central amygdala, respectively.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R614

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