右美托咪定缓解大鼠周围神经病理性疼痛的机制  

The Mechanism of Dexmedetomidine Relieving Neuropathic Pain of Peripheral Nerve in the Rats

作　　者：史艳燕 王勇[1] 舒英 余聪 彭晓红[1] 罗高平[1] 

机构地区：[1]华中科技大学同济医学院附属普爱医院麻醉科,武汉430033

出　　处：《华中科技大学学报（医学版）》2017年第6期665-668,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省卫生计生委科研基金资助项目(No.WJ2015MB153);武汉市卫生计生委科研基金资助项目(No.WX15C25)

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(1μg/kg)。每组于术前1d、术后1、3、7、14d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 Totally,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 aesthesiometer.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 operation,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 observation.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% and206% and then the expression levels of BDNF(0.66±0.36)and NF-κB(0.02±0.08)in SNI+Dex group were decreased significantly 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.

关 键 词：神经病理性疼痛 脑源性神经营养因子 核因子-ΚB 右美托咪定 

分 类 号：R745[医药卫生—神经病学与精神病学]