低浓度布比卡因对QX-314-OH神经阻滞的初步药理学研究
发布时间：2019-06-20 20:47
【摘要】：目的:QX-314是利多卡因的四价阳离子衍生物。辣椒素能激活TRPV1通道,QX-314经过此通道进入神经细胞阻滞钠离子通道,产生持久的痛觉阻滞,且运动功能不受影响。QX-314这种选择性阻断痛觉的特性非常适用于临床镇痛,但辣椒素有直接的疼痛刺激及神经毒性。文献报道布比卡因也是TRPV1通道的激动剂,可用于替代辣椒素。QX-314-OH是新合成的QX-314羟基化合物,预实验发现其神经毒性较QX-314低,推测布比卡因与QX-314-OH合用可以产生理想的效果,但由于局麻药的神经毒性呈剂量依赖关系,因此两药的浓度选择显得极为关键。预实验发现布比卡因提高QX-314-OH的神经阻滞效果的最低有效浓度为0.0375%,本实验拟测定QX-314-OH在大鼠坐骨神经阻滞的半数有效浓度和最低有效浓度;并选择0.0375%布比卡因,联合不同浓度的QX-314-OH,观察神经阻滞效果,并进行神经病理学观察,验证其安全性。旨在寻找安全、理想的布比卡因和QX-314-OH的配比浓度,为QX-314-OH的深入研究提供参考。方法:采用大鼠坐骨神经阻滞模型,用BLISS法,测定QX-314-OH对感觉、运动神经阻滞的EC_(50)。选择最低有效浓度和半数有效浓度之间不同浓度的QX-314-OH,分别复合0.0375%布比卡因,观察各组神经阻滞的有效率、起效时间和持续时间;并在光镜下观察HE染色坐骨神经标本,了解是否存在病理学损伤及其损伤程度,初步判断其安全性。结果:1.QX-314-OH对感觉(精细触觉、痛觉)和运动神经阻滞的最低有效浓度均为10 m M;感觉(精细触觉、痛觉)和运动阻滞的半数有效浓度分别为(13 m M、19 m M)和27 m M。2.QX-314-OH联合布比卡因:0.0375%布比卡因复合QX-314-OH与单用QX-314-OH相比较,对感觉、运动神经的阻滞有统计学差异,复合组有效率较高,且作用时间更长。3.与布比卡因合用时,不同浓度的Q-X314-OH体现出不同的阻滞特点:10、15 m M QX-314-OH复合0.0375%布比卡因,感觉阻滞时间明显大于运动阻滞时间;5、20、25 m M浓度时,感觉与运动阻滞时间无显著性差异。4.神经毒性观察:每组各时期坐骨神经无明显损伤,未见神经脱髓鞘、坏死等;但个别组在第1天坐骨神经有不同程度炎性细胞浸润,而在第3天、7天、15天坐骨神经无明显的炎性细胞浸润。结论:1.0.0375%的布比卡因可显著提高QX-314-OH起效率,并能延长QX-314-OH神经阻滞时间,其阻滞时间随QX-314-OH浓度的增加而延长;在特定的浓度,复合运用可以产生选择性痛觉阻滞。2.QX-314-OH单独应用,以及与低浓度的布比卡因合用,均无明显的神经毒性。
[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.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R96
本文编号：2503519
[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.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R96
【相似文献】
中国硕士学位论文全文数据库 前2条
1 马龙翔;季胺类局麻药QX-314-OH与左旋布比卡因合用的作用机制研究[D];昆明医科大学;2016年
2 李俊;低浓度布比卡因对QX-314-OH神经阻滞的初步药理学研究[D];川北医学院;2016年
，本文编号：2503519
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