右美托咪定缓解大鼠周围神经病理性疼痛的机制

摘要

目的 研究神经病理性疼痛大鼠脊髓中脑源性神经营养因子(BDNF)和核因子-κB(NF-κB)的表达变化,探讨右美托咪定(Dex)缓解大鼠周围神经病理性疼痛的机制.方法 雌性SD大鼠24只,随机分为4组(n=6):Sham+ NS、Sham+Dex组、SNI+NS组和SNI+Dex组.Sham组实施假手术,SNI组建立坐骨神经分支选择性损伤模型,随后分别鞘内注射等量的生理盐水(NS)和Dex(1 μg/kg).每组于术前1 d、术后1、3、7、14 d测定机械性痛阈(MWT).免疫组织化学法检测脊髓BDNF和NF-κB的表达,Western blot法检测Dex处理后BDNF和NF-κB蛋白表达变化.结果 从术后第3天起,SNI+NS组所有大鼠均出现了持续的机械性痛觉异常.免疫组化检测结果显示:BDNF和 NF-κB散在表达于脊髓,BDNF主要表达在细胞质,而NF-κB主要表达在细胞核,以脊髓背角Ⅰ ~ Ⅳ层和背角深层Ⅴ ~ Ⅵ层表达较多,手术侧多于非手术侧.Western blot检测结果显示:在SNI+ NS组中BDNF和NF-κB蛋白的表达水平分别为(1.11 ± 0.56)、(2.31 ± 0.46),明显高于Sham+NS组的(0.72 ± 0.26)和(0.01 ± 0.06),分别增加53% 和206%;SNI+Dex组中BDNF和NF-κB蛋白的表达分别为(0.66 ± 0.36)、(0.02 ± 0.08),与SNI+ NS组相比明显降低(均 P<0.05).结论 Dex 通过降低BDNF 和NF-κB 表达缓解神经病理性疼痛.%Objective To investigate the mechanism of dexmedetomidine(Dex)relieving neurologic pain by studying the changes of brain-derived neurotrophic factor(BDNF)and NF-κB in the spinal cord of the neurologic pain rats.Methods Total-ly,24 female SD rats were randomly divided into four groups,including Sham+NS group,Sham+Dex group,SNI+NS group, and SNI+Dex group(n=6 each group).Sham group suffered from no nerve damage.In SNI groups,surgery was performed for SNI neuropathic pain model.Mechanical withdrawal threshold was measured by an automated dynamic plantar aesthesiome-ter.The expression levels of BDNF and NF-κB in the spinal cord of rats were detected by immunohistochemistry.The effect of Dex treatment on protein expression of BDNF and NF-κB was analyzed by Western blotting.Results Since the day 3 after oper-ation,all rats in group SNI+NS developed a relative unchangeable mechanical allodynia.Immunohistochemistry results showed that the expression of BDNF was located mainly in cytoplasm in astrocyte and NF-κB in neuron according to morphologic obser-vation.The expression levels of BDNF and NF-κB in the operation side were higher than those in the non-operation side.Western blot analysis indicated that the expression levels of BDNF(1.11 ± 0.56)and NF-κB(2.31 ± 0.46)in SNI+ NS group were increased significantly as compared with Sham +NS group(0.72 ± 0.26)and(0.01 ± 0.06)by the ratio of 53% and 206% and then the expression levels of BDNF(0.66 ± 0.36)and NF-κB(0.02 ± 0.08)in SNI+Dex group were decreased signifi-cantly as compared with SNI+ NS group(1.11 ± 0.56)and(2.31 ± 0.46)(P<0.05).Conclusion Dex attenuates neuropathic pain in SNI model by suppressing BDNF expression in astrocytes and NF-κB activity in neurons.