敬钊缨毛蛛毒素-V对治疗CCI大鼠神经病理性疼痛的研究

发布时间：2018-05-12 04:36

本文选题：敬钊缨毛蛛毒素-Ⅴ + 坐骨神经慢性压迫模型　；参考：《中南大学》2014年硕士论文

【摘要】：目的：研究鞘内注射敬钊缨毛蛛毒素-V对大鼠坐骨神经慢性压迫损伤性神经病理性疼痛的作用,为敬钊缨毛蛛毒素-V治疗神经病理性疼痛提供实验依据。方法：选择成年健康雄性SD大鼠60只,体重250-300g,随机分成6组(n=10)：对照组：单纯CCI处理组(N组)；CCI+硬膜外置管+鞘内注射盐水组：(ctrl组)；CCI+硬膜外置管+鞘内注射吗啡组：(M组)；敬钊缨毛蛛毒素-V (JZTX-V)实验组：CCI+硬膜外置管+鞘内注射JZTX-V组,该组分为三组：鞘内注射20μg/kg JZTX-V (J1组)；鞘内注射40μg/kg JZTX-V(J2组)；鞘内注射60μg/kg JZTX-V(J3组)。手术处理前一天测基础机械痛阂值。除N组只做CCI外,其余各组行处理均行CCI+硬膜外置管处理,将各组不合要求的大鼠予以剔除,术后3天、5天、7天测定机械痛阈值并观察大鼠的行为学表现,术后第7天除N组外,其余各组术后经鞘内置管分别注入生理盐水、吗啡或不同剂量JZTX-V,注射完毕后0.5h、1h、1.5h、2h分别完成机械痛阈的测定。给药后比较各组大鼠的痛阈值的差异,并比较各组大鼠的不良反应。结果： 1.N组中因术中麻醉过量致死1只,术后发现大鼠术侧后肢瘫痪1只；CCI+鞘内置管各组中,术中出现死亡2只,术后第1-2天出现死亡4只,术后第二天瘫痪4只,其余大鼠行为表现较术前无特殊改变。各组大鼠术后的机械痛阈值较基础痛阈值明显下降(P0.05),其中同一时点N组与CCI+鞘内置管各组术后机械痛阈值下降水平无差异(P0.05)。 2.给药后同一时点,M、J1、J2、J3组与ctrl组相比,大鼠机械痛阈值均升高(P0.05)。M组给药后1h大鼠机械痛阈值达到高峰,给药后2h大鼠机械痛阈值恢复到给药前水平,J、J2组给药后1h大鼠的机械痛阈达到高峰,给药后2h大鼠的机械痛阈依然高于给药前水平。J3组在给药后1.5h大鼠的机械痛阈达到高峰,给药后2h机械痛阈值高于给药前水平,并且高于J组,与J2组持平。 3.给药后同一时点,J1、J2、J3组相比,大鼠机械痛阈值J3J2J1(P0.05)。 4.J3组药物在最佳镇痛活性的时间点,大鼠机械痛阈值水平不及M组(P0.05),但大鼠的机械痛阈下降较M组缓慢。 5.鞘注JZTX-V对大鼠的运动机能未见明显影响,大鼠正常采食,肢体运动等日常活动情况较给药前未见明显变化,未出现死亡情况,证明鞘注JZTX-V有一定的实验安全性。结论： 1.鞘注JZTX-V可以缓解CCI大鼠机械痛敏反应,产生明显的镇痛效应,镇痛效应呈现明显的剂量效应。 2.鞘注JZTX-V对CCI大鼠机械痛的镇痛作用效果与吗啡相比,在表现出最佳镇痛活性的时间点JZTX-V的作用强度不如吗啡,但其镇痛作用持续时间较吗啡长。 3.鞘注JZTX-V对大鼠运动无明显影响,实验安全性较高。 4. JZTX-V可作为治疗神经病理性疼痛的一种有效方法,同时可为进一步研发神经病理性疼痛药物提供新的思路与方法。
[Abstract]:Objective: to study the effect of intrathecal injection of Spider toxin V on neuropathic pain caused by chronic compression of sciatic nerve in rats, and to provide experimental evidence for the treatment of neuropathic pain. Methods: sixty adult male SD rats were selected. Weighing 250-300g, randomly divided into 6 groups: control group: CCI treatment group: control group; JZTX-V group was injected intrathecally with external tube. This group was divided into three groups: intrathecal injection of 20 渭 g/kg JZTX-V J1, intrathecal injection of 40 渭 g/kg JZTX-V(J2, intrathecal injection of 60 渭 g/kg JZTX-V(J3. The threshold of basic mechanical pain was measured one day before surgical treatment. With the exception of CCI in group N, the other groups were treated with CCI epidural catheterization. The rats in each group were excluded. The threshold of mechanical pain was measured 3 days, 5 days and 7 days after operation, and the behavior of the rats was observed. On the 7th day after operation, the other groups were injected with saline, morphine or different doses of JZTX-V through intrathecal tube respectively. The mechanical pain threshold was measured at 1 hour and 1.5 h after injection. The difference of pain threshold and adverse reaction of each group were compared after administration. Results: 1.Intraoperative anesthetic overdose killed 1 rat in group N, one rat with intrathecal catheterization of CCI was found after operation, 2 rats died during operation, 4 rats died on day 1-2 after operation, and 4 rats were paralyzed the next day after operation, 2 rats died during the operation, 4 rats died on the second day after operation. There were no special changes in the behavior of the other rats. The mechanical pain threshold of each group was significantly lower than that of the basic pain threshold, and there was no difference in the level of mechanical pain threshold between the N group and the CCI sheath placement group at the same time point. 2. Compared with the ctrl group, the mechanical pain threshold of the rats in the MJ1J2J2J3 group was higher than that in the P0.05 group at the same time point after administration, and the mechanical pain threshold reached the peak at 1 hour after administration in the P0.05U. M group. The mechanical pain threshold of JNJ _ 2 group reached its peak at 1 h after administration, and the mechanical pain threshold of group J _ 3 was still higher than that of the rats in group J _ 3 at 1.5 h after administration, and the mechanical pain threshold of group J _ (3) was still higher than that of group J _ (3) at 1 h after administration of the drug, and the mechanical pain threshold of group JJ _ (3) was still higher than that of group J _ (3) at 1.5 h after administration. The mechanical pain threshold at 2 h after administration was higher than that before administration and higher than that in group J, which was the same as that in group J 2. 3. At the same time after administration, the mechanical pain threshold of J3J2J1 / J3 group was higher than that of J3J2J1 group (P0.05). At the time point of optimal analgesic activity, the mechanical pain threshold level in 4.J3 group was lower than that in M group (P 0.05), but the decrease of mechanical pain threshold was slower in 4.J3 group than in M group. 5. There was no obvious effect of JZTX-V on the motor function of the rats. The daily activities such as normal feeding, limb movement and so on did not change obviously, and there was no death in the rats. It was proved that the sheath injection of JZTX-V had certain experimental safety. Conclusion: 1. Intrathecal injection of JZTX-V alleviated the mechanical pain sensitivity of CCI rats and produced a significant analgesic effect, and the analgesic effect showed a significant dose effect. 2. Compared with morphine, the analgesic effect of JZTX-V on mechanical pain of CCI rats was not as strong as that of morphine, but the analgesic effect of JZTX-V was longer than that of morphine. 3. Sheath injection of JZTX-V had no obvious effect on the movement of rats, and the experiment was safe. 4. JZTX-V can be used as an effective method for the treatment of neuropathic pain, and it can also provide new ideas and methods for further research and development of neuropathic pain drugs.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R741

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