α-硫辛酸对紫杉醇诱发的大鼠外周神经病的治疗作用

EFFECTS OF α-LIPOIC ACID ON PACLITAXEL INDUCED PERIPHERAL NEUROPATHY in RATS

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2mg/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α-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-κB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,4 g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阈下降、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。

Objective： To establish paclitaxel induced peripheral neuropathy model of rats. To investigate effects of a-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-v,B 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-~cB 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 D 14 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 4 g and 15 g yon 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-vd3 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-v,B in spinal dorsal horn and dorsal root ganglion in four groups. Conclusion： Pre-treatment of paclitaxel induced peripheral neuropathy rats with a-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.