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  本文選題：敬釗纓毛蛛毒素-Ⅴ + 坐骨神經(jīng)慢性壓迫模型��； 參考：《中南大學》2014年碩士論文

【摘要】：目的：研究鞘內(nèi)注射敬釗纓毛蛛毒素-V對大鼠坐骨神經(jīng)慢性壓迫損傷性神經(jīng)病理性疼痛的作用,為敬釗纓毛蛛毒素-V治療神經(jīng)病理性疼痛提供實驗依據(jù)。 方法：選擇成年健康雄性SD大鼠60只,體重250-300g,隨機分成6組(n=10)：對照組：單純CCI處理組(N組)；CCI+硬膜外置管+鞘內(nèi)注射鹽水組：(ctrl組)；CCI+硬膜外置管+鞘內(nèi)注射嗎啡組：(M組)；敬釗纓毛蛛毒素-V (JZTX-V)實驗組：CCI+硬膜外置管+鞘內(nèi)注射JZTX-V組,該組分為三組：鞘內(nèi)注射20μg/kg JZTX-V (J1組)；鞘內(nèi)注射40μg/kg JZTX-V(J2組)；鞘內(nèi)注射60μg/kg JZTX-V(J3組)。手術(shù)處理前一天測基礎(chǔ)機械痛閡值。除N組只做CCI外,其余各組行處理均行CCI+硬膜外置管處理,將各組不合要求的大鼠予以剔除,術(shù)后3天、5天、7天測定機械痛閾值并觀察大鼠的行為學表現(xiàn),術(shù)后第7天除N組外,其余各組術(shù)后經(jīng)鞘內(nèi)置管分別注入生理鹽水、嗎啡或不同劑量JZTX-V,注射完畢后0.5h、1h、1.5h、2h分別完成機械痛閾的測定。給藥后比較各組大鼠的痛閾值的差異,并比較各組大鼠的不良反應。 結(jié)果： 1.N組中因術(shù)中麻醉過量致死1只,術(shù)后發(fā)現(xiàn)大鼠術(shù)側(cè)后肢癱瘓1只；CCI+鞘內(nèi)置管各組中,術(shù)中出現(xiàn)死亡2只,術(shù)后第1-2天出現(xiàn)死亡4只,術(shù)后第二天癱瘓4只,其余大鼠行為表現(xiàn)較術(shù)前無特殊改變。各組大鼠術(shù)后的機械痛閾值較基礎(chǔ)痛閾值明顯下降(P0.05),其中同一時點N組與CCI+鞘內(nèi)置管各組術(shù)后機械痛閾值下降水平無差異(P0.05)。 2.給藥后同一時點,M、J1、J2、J3組與ctrl組相比,大鼠機械痛閾值均升高(P0.05)。M組給藥后1h大鼠機械痛閾值達到高峰,給藥后2h大鼠機械痛閾值恢復到給藥前水平,J、J2組給藥后1h大鼠的機械痛閾達到高峰,給藥后2h大鼠的機械痛閾依然高于給藥前水平。J3組在給藥后1.5h大鼠的機械痛閾達到高峰,給藥后2h機械痛閾值高于給藥前水平,并且高于J組,與J2組持平。 3.給藥后同一時點,J1、J2、J3組相比,大鼠機械痛閾值J3J2J1(P0.05)。 4.J3組藥物在最佳鎮(zhèn)痛活性的時間點,大鼠機械痛閾值水平不及M組(P0.05),但大鼠的機械痛閾下降較M組緩慢。 5.鞘注JZTX-V對大鼠的運動機能未見明顯影響,大鼠正常采食,肢體運動等日常活動情況較給藥前未見明顯變化,未出現(xiàn)死亡情況,證明鞘注JZTX-V有一定的實驗安全性。 結(jié)論： 1.鞘注JZTX-V可以緩解CCI大鼠機械痛敏反應,產(chǎn)生明顯的鎮(zhèn)痛效應,鎮(zhèn)痛效應呈現(xiàn)明顯的劑量效應。 2.鞘注JZTX-V對CCI大鼠機械痛的鎮(zhèn)痛作用效果與嗎啡相比,在表現(xiàn)出最佳鎮(zhèn)痛活性的時間點JZTX-V的作用強度不如嗎啡,但其鎮(zhèn)痛作用持續(xù)時間較嗎啡長。 3.鞘注JZTX-V對大鼠運動無明顯影響,實驗安全性較高。 4. JZTX-V可作為治療神經(jīng)病理性疼痛的一種有效方法,同時可為進一步研發(fā)神經(jīng)病理性疼痛藥物提供新的思路與方法。
[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.
【學位授予單位】：中南大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R741

【參考文獻】

相關(guān)期刊論文 前1條

1 曾雄智;鄧梅春;孫正華;王賢純;梁宋平;;敬釗毒素-Ⅴ的合成、復性及其鉀通道活性鑒定[J];中國生物化學與分子生物學報;2008年05期

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本文編號：1877125