發(fā)布時間：2019-06-20 20:47

【摘要】：目的:QX-314是利多卡因的四價陽離子衍生物。辣椒素能激活TRPV1通道,QX-314經(jīng)過此通道進入神經(jīng)細胞阻滯鈉離子通道,產(chǎn)生持久的痛覺阻滯,且運動功能不受影響。QX-314這種選擇性阻斷痛覺的特性非常適用于臨床鎮(zhèn)痛,但辣椒素有直接的疼痛刺激及神經(jīng)毒性。文獻報道布比卡因也是TRPV1通道的激動劑,可用于替代辣椒素。QX-314-OH是新合成的QX-314羥基化合物,預(yù)實驗發(fā)現(xiàn)其神經(jīng)毒性較QX-314低,推測布比卡因與QX-314-OH合用可以產(chǎn)生理想的效果,但由于局麻藥的神經(jīng)毒性呈劑量依賴關(guān)系,因此兩藥的濃度選擇顯得極為關(guān)鍵。預(yù)實驗發(fā)現(xiàn)布比卡因提高QX-314-OH的神經(jīng)阻滯效果的最低有效濃度為0.0375%,本實驗擬測定QX-314-OH在大鼠坐骨神經(jīng)阻滯的半數(shù)有效濃度和最低有效濃度;并選擇0.0375%布比卡因,聯(lián)合不同濃度的QX-314-OH,觀察神經(jīng)阻滯效果,并進行神經(jīng)病理學(xué)觀察,驗證其安全性。旨在尋找安全、理想的布比卡因和QX-314-OH的配比濃度,為QX-314-OH的深入研究提供參考。方法:采用大鼠坐骨神經(jīng)阻滯模型,用BLISS法,測定QX-314-OH對感覺、運動神經(jīng)阻滯的EC_(50)。選擇最低有效濃度和半數(shù)有效濃度之間不同濃度的QX-314-OH,分別復(fù)合0.0375%布比卡因,觀察各組神經(jīng)阻滯的有效率、起效時間和持續(xù)時間;并在光鏡下觀察HE染色坐骨神經(jīng)標本,了解是否存在病理學(xué)損傷及其損傷程度,初步判斷其安全性。結(jié)果:1.QX-314-OH對感覺(精細觸覺、痛覺)和運動神經(jīng)阻滯的最低有效濃度均為10 m M;感覺(精細觸覺、痛覺)和運動阻滯的半數(shù)有效濃度分別為(13 m M、19 m M)和27 m M。2.QX-314-OH聯(lián)合布比卡因:0.0375%布比卡因復(fù)合QX-314-OH與單用QX-314-OH相比較,對感覺、運動神經(jīng)的阻滯有統(tǒng)計學(xué)差異,復(fù)合組有效率較高,且作用時間更長。3.與布比卡因合用時,不同濃度的Q-X314-OH體現(xiàn)出不同的阻滯特點:10、15 m M QX-314-OH復(fù)合0.0375%布比卡因,感覺阻滯時間明顯大于運動阻滯時間;5、20、25 m M濃度時,感覺與運動阻滯時間無顯著性差異。4.神經(jīng)毒性觀察:每組各時期坐骨神經(jīng)無明顯損傷,未見神經(jīng)脫髓鞘、壞死等;但個別組在第1天坐骨神經(jīng)有不同程度炎性細胞浸潤,而在第3天、7天、15天坐骨神經(jīng)無明顯的炎性細胞浸潤。結(jié)論:1.0.0375%的布比卡因可顯著提高QX-314-OH起效率,并能延長QX-314-OH神經(jīng)阻滯時間,其阻滯時間隨QX-314-OH濃度的增加而延長;在特定的濃度,復(fù)合運用可以產(chǎn)生選擇性痛覺阻滯。2.QX-314-OH單獨應(yīng)用,以及與低濃度的布比卡因合用,均無明顯的神經(jīng)毒性。
[Abstract]:Objective: QX-314 is a tetravalent cationic derivative of lidocaine. Capsaicin can activate TRPV1 channel, through which QX-314 enters nerve cells to block sodium channel, resulting in lasting pain block, and motor function is not affected. QX-314 is very suitable for clinical analgesia, but capsaicin has direct pain stimulation and neurotoxicity. It has been reported that bupivacaine is also an agonist of TRPV1 channel, which can be used to replace capsaicin. QX-314-OH is a newly synthesized QX-314 hydroxyl compound. The neurotoxicity of bupivacaine combined with QX-314-OH is lower than that of QX-314. It is speculated that the combination of bupivacaine and QX-314-OH can produce ideal results, but because the neurotoxicity of local anesthetics is dose-dependent, the concentration selection of the two drugs is very important. It was found that the minimum effective concentration of bupivacaine to improve the nerve block effect of QX-314-OH was 0.0375%. The aim of this experiment was to determine the half effective concentration and the lowest effective concentration of QX-314-OH in rat sciatica block, and 0.0375% bupivacaine was selected to observe the effect of nerve block with different concentrations of QX-314-OH, and the neuropathological observation was carried out to verify its safety. The purpose of this paper is to find a safe and ideal concentration of bupivacaine and QX-314-OH, and to provide reference for the further study of QX-314-OH. Methods: the EC_ (50) of QX-314-OH on sensory and motor nerve block was measured by BLISS method. Different concentrations of QX-314-OH, between the lowest effective concentration and half effective concentration were combined with 0.0375% bupivacaine respectively to observe the effective rate, onset time and duration of nerve block in each group, and to observe the specimens stained with HE under light microscope to find out whether there was pathological injury and the degree of injury, and to judge its safety. Results: the minimum effective concentration of 1.QX-314-OH for sensory (fine tactile, pain) and motor nerve block was 10 mm. The 50% effective concentrations of sensory (fine tactile, pain) and motor block were (13 mm, 19 m M) and 27 m M.2.QX-314-OH combined with bupivacaine: 0.0375% bupivacaine combined with QX-314-OH alone). There was significant difference in sensory and motor nerve block between the two groups. The effective rate of sensory and motor nerve block was higher and the action time was longer than that of bupivacaine combined with bupivacaine alone. When combined with bupivacaine, different concentrations of Q-X314-OH showed different blocking characteristics: 10, 15 mm QX-314-OH combined with 0.0375% bupivacaine, sensory block time was significantly longer than motor block time, 5, 20, 25 mm concentration, sensory and motor block time had no significant difference. 4. Observation of neurotoxicity: there was no obvious injury, no demyelination, necrosis and so on in each group, but there was different degree of inflammatory cell infiltration in some groups on the first day, but no obvious inflammatory cell infiltration was found on the 3rd, 7th and 15th day. Conclusion: 1.0.0375% bupivacaine can significantly improve the starting efficiency of QX-314-OH and prolong the nerve block time of QX-314-OH, and the blocking time can be prolonged with the increase of QX-314-OH concentration, and selective pain block can be produced at specific concentration. 2.QX-314-OH alone and in combination with low concentration of bupivacaine have no obvious neurotoxicity.
【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R96

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1 馬龍翔;季胺類局麻藥QX-314-OH與左旋布比卡因合用的作用機制研究[D];昆明醫(yī)科大學(xué);2016年

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本文編號：2503519