【作者】 李君； 冯艺； 王莹； 张挺杰；

【Author】 LI Jun,FENG Yi,WANG Ying,ZHANG Ting Jie.Department of Anesthesiology and Pain Medicine, People’s Hospital of Peking University,Beijing 100044,China

【机构】 北京大学人民医院麻醉疼痛科；

【摘要】 目的建立紫杉醇诱发大鼠周围神经疾病的模型,研究NF-κB在紫杉醇诱发大鼠周围神经疾病中的变化。方法健康雄性SD大鼠20只,随机分为紫杉醇组(P组)和对照组(C组),每组10例。分别隔日腹腔内注射紫杉醇2mg/kg(P组)或等量生理盐水(C组),共4次。建模前和建模后第7天、第14天和第21天分别测量大鼠的机械痛阈和热痛阈。第21天时免疫荧光法测定L4~6节段脊髓背角NF-κB的表达及星型胶质细胞的数量,Western blot法测量L4~6脊髓背角和背根神经节(DRG)中NF-κB的含量。结果紫杉醇组与对照组相比有体重下降的趋势。D14和D21紫杉醇组的热痛阈显著低于对照组(P<0.05)。紫杉醇组D7、D14、D21的热痛阈依次下降(P<0.05)。紫杉醇组D14和D21的4g和15g von Frey纤维刺激缩足反应大鼠显著多于对照组(P<0.05)。紫杉醇组大鼠脊髓背角中星型胶质细胞的数量明显低于对照组(P<0.00 1)。对照组NF-κB主要在大鼠脊髓背角星型胶质细胞的胞浆中表达,紫杉醇组NF-κB主要在大鼠脊髓背角星型胶质细胞的细胞核内表达。L4~6脊髓背角和DRG中NF-κB的含量差异无统计学意义。结论给予紫杉醇后大鼠出现机械痛阈和热痛阈下降、脊髓背角的星型胶质细胞数量减少、NF-κB被激活。提示星型胶质细胞以及NF-κB可能在紫杉醇诱发大鼠周围神经疾病模型中发挥了重要作用。更多还原

【Abstract】 Objective To establish paclitaxel induced peripheral neuropathy model of rats.To investigate changes of NF-κB in paclitaxel induced peripheral neuropathy of rats.Method Twenty healthy SD rats were randomly divided into paclitaxel group(P group) and control group(C group),ten rats of each group.Paclitaxel 2mg/kg ip every other day(P group) and equal volume of saline(C group),4 times total.Test mechanical pain threshold and heat pain threshold on DO,D7,D14 and D 21.Immunofluorescence of NF-κB and astrocytes in spinal dorsal horn of L4~6 were tested on D21.Levels of NF-κB in spinal dorsal horn and DRG of L4~6 on D21 were tested by Western blot.Result There was a trend of reducing of weight of P group comparing with C group.Heat pain threshold of P group on D14 and D21 was significantly lower than C group(p<0.05).Paw withdraws of 4g and 15g von Frey fiber in P group on D14 and D21 were significantly higher than C group(p<0.05).Counts of astrocytes in spinal dorsal horn in P group were significantly lower than C group(p<0.001).NF-κB predominantly expressed in cytoplasma of astrocytes in spinal dorsal horn in C group, while expressed in nucleus in P group.No statistical difference of levels of NF-κB in spinal dorsal horn and DRG in both groups.Conclusion Down regulation of mechanical and heat pain threshold,decreases of astrocytes in spinal dorsal horn, activation of NF-κB after administration of paclitaxel,which indicated that astrocytes and NF-κB may play a role in paclitaxel induced peripheral neuropathy model of rats.更多还原