發(fā)布時間：2018-05-22 09:24

  本文選題：右美托咪定 + 羅哌卡因　； 參考：《第四軍醫(yī)大學》2015年碩士論文

【摘要】：研究背景:需要手術治療的患者常常處于強烈的應激環(huán)境之中,因局麻藥導致的不良反應的發(fā)生會加劇患者的精神壓力,對患者的康復極為不利,甚至會危及生命安全。羅哌卡因是一種新型的酰胺類局部麻醉藥,它較其他同類局麻藥更為安全,而且毒副反應少,但因其過量使用或誤入血管而造成的因血藥濃度過高而出現的不良反應也屢見不鮮。局麻藥所導致的中樞神經系統(tǒng)毒性,在臨床上最為常見的并發(fā)癥如驚厥,嚴重者甚至可以危及生命,而驚厥控制后的患者也常常表現出焦慮、抑郁等負性情緒,這些都直接影響患者預后和醫(yī)療體驗。那么,臨床上有沒有一種藥物既能有效地預防驚厥的發(fā)生又能合理的改善不良反應造成的負性情緒呢?咪達唑侖是目前用于控制和預防局麻藥致驚厥的經典藥物,但反復、大劑量的靜脈內用藥所致的呼吸抑制是其嚴重致死性不良反應。右美托咪定是一種新型的高選擇性α2-腎上腺素受體激動劑,能產生滿意的鎮(zhèn)靜及鎮(zhèn)痛效果,而且對自主呼吸無明顯的影響,目前已廣泛應用于圍術期鎮(zhèn)靜、鎮(zhèn)痛和臟器保護的臨床實踐。但右美托咪定預處理是否能有效預防局麻藥導致的驚厥,且其能否改善驚厥后的負性情緒及其作用機理都是亟待我們解決的問題。實驗目的:本實驗擬觀察劑量梯度右美托咪定預處理對羅哌卡因致驚厥及驚厥后負性情緒的影響,探討右美托咪定對基底外側杏仁核與中央杏仁核p-ERK表達的影響在羅哌卡因致驚厥及驚厥后負性情緒中的作用。方法:本實驗第一部分擬采用行為藥理學的方法,通過離線視屏記錄評估小鼠驚厥行為,探討不同劑量右美托咪定預處理對羅哌卡因致驚厥的半數致驚厥劑量的影響。第二部分擬綜合采用行為藥理學、免疫組織化學和分子生物學的方法探討不同劑量右美托咪定預處理對各半數致驚厥劑量羅哌卡因誘導的驚厥及驚厥后小鼠的負性情緒的影響,及其在驚厥后2 h基底外側杏仁核和驚厥后24 h時中央杏仁核內p-ERK表達的影響。結果:本實驗結果表明:2.4、4.8和9.6μg/kg右美托咪定預處理可劑量依賴性地(1)增加21.72%、25.70%和41.98%羅哌卡因的半數致驚厥劑量;(2)延長半數致驚厥劑量羅哌卡因致驚厥的驚厥潛伏期,并縮短驚厥持續(xù)時間;(3)增加曠場試驗中小鼠中央區(qū)域活動時間百分比和高架十字迷宮試驗中開臂停留時間百分比及開臂進入次數百分比,提示其呈可劑量依賴性改善驚厥后的焦慮/抑郁樣負性情緒;(4)抑制驚厥后2 h時基底外側杏仁核及驚厥后24 h時中央杏仁核內p-ERK的過表達。結論:基于以上實驗結果,我們認為右美托咪定預處理可劑量依賴性地改善羅哌卡因致驚厥的發(fā)生及驚厥后的負性情緒,該保護作用可能分別與其抑制基底外側杏仁核和中央杏仁核內p-ERK的過表達有關。
[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 偽 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.
【學位授予單位】：第四軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R614

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本文編號：1921503