Objective: To establish paclitaxel induced peripheral neuropathy model of rats. To investigate effects of α-lipoic acid on paclitaxel induced peripheral neuropathy in rats. Methods: Forty SD rats were randomly divided into paclitaxel group (group P), control group (group C), pre-treatment group (group AP) and post-treatment group (group PA), ten rats in each group. Rats were injected with paclitaxel 2 mg/kg (P group, AP group and PA group) and equal volume of saline (group C) ip, qod, 4 times total. Rats were injected with a-lipoic acid 25 mg/kg (ip, qd) at D0-D6 (group AP) and D21-D27 (group PA). Mechanical pain threshold and heat pain threshold were tested at DO, D7, D14, D21 and D28. Immunofluorescence of NF-kB and astrocytes in spinal dorsal horn of L4-6 was tested on D21 (group C, P and AP) and D28 (group PA). Levels of NF-kB in mechanical spinal dorsal horn and DRG of L4-6 were tested by Western blot on the same time points. Results: Heat pain threshold of group P on D14 and D21 was significantly lower than group C. Paw withdrawal rate of 4 g and 15 g von Frey fiber in group P on D14 and D21 were significantly higher than group C. Heat pain threshold of group AP on D14 and D21 was significantly higher than group P. Paw withdrawal rate of 4g and 15 g von Frey fiber in group AP on D14 and D21 were significantly lower than group P. Counts of astrocytes in spinal dorsal horn in group P were significantly lower than group C and significantly higher than group AP. NF-kB predominantly expressed in cytoplasma of astrocytes in spinal dorsal horn in group C and group AP, while expressed both in nuclei and cytoplasma in group P and group PA. No statistical difference of NF-kB in spinal dorsal horn and dorsal root ganglion in four groups. Conclusion: Pre-treatment of paclitaxel induced peripheral neuropathy rats with α-lipoic acid inhibited the down regulation of heat pain threshold, hyperalgesia, allodynia, increases of astrocytes in spinal dorsal horn and inhibites abnormal activation of NF-kB.%目的:建立紫杉醇诱发大鼠周围神经疾病的模型,研究α-硫辛酸对紫杉醇诱发大鼠周围神经疾病的治疗作用.方法:40只SD大鼠随机平均分为紫杉醇组(P组)、对照组(C组)、预治疗组(AP组)和后治疗组(PA组).四组分别隔日给予紫杉醇2 mg/kg(P组、AP组和PA组)或等量生理盐水(C组)ip,共4次.AP组和PA组分别于D0-D6和D21-D27给予a-硫辛酸25 mg/kg (ip,qd).D0、D7、D14、D21和D28分别测量大鼠的机械痛阈和热痛阈、脊髓背角NF-kB的表达及星型胶质细胞的数量、脊髓背角和背根神经节中NF-κB的含量.结果:P组D14和D21的热痛阈显著低于C组,4g和15 g von Frey纤维刺激缩足反应显著高于C组.AP组D14和D21的热痛阈显著高于P组,4g和15 g von Frey纤维刺激缩足反应显著低于P组.P组脊髓背角中星型胶质细胞的数量显著低于C组.AP组脊髓背角中星型胶质细胞的数量显著高于P组.C组和AP组NF-κB主要在脊髓背角星型胶质细胞的细胞浆中表达.P组和PA组NF-κB在脊髓背角星型胶质细胞的细胞核和细胞浆内同时表达.四组NF-κB在脊髓和背根神经节内的表达差异无显著意义.结论:预防性给予α-硫辛酸对紫杉醇诱发大鼠周围神经疾病模型中的热痛阁下降、痛觉过敏、痛觉超敏的减少,脊髓背角星型胶质细胞数量增加和NF-κB异常激活的抑制.
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