脊髓内高迁移率蛋白-1参与背根节慢性压迫大鼠机械性痛敏的机制  

High-mobility group box 1 in the spinal cord contributes to mechanical allodynia in a rat model of chronic compression of dorsal root ganglion

作　　者：张涛[1] 陈磊 王松涛[1] 江莉祥 李明[3] 李涛[4] 

机构地区：[1]武警北京总队医院医务处,北京100027 [2]武警天津总队第一支队,天津300222 [3]武警北京总队医院内一科,北京100027 [4]武警北京总队医院急诊科,北京100027

出　　处：《神经解剖学杂志》2013年第3期333-337,共5页Chinese Journal of Neuroanatomy

摘　　要：目的:观察背根节慢性压迫(chronic compression of dorsal root ganglion,CCD)大鼠脊髓内高迁移率蛋白-1(high mobility group box-1,HMGB1)的变化,探讨其参与痛觉信息传递的机制,为慢性痛的治疗提供新的思路和靶点。方法:(1)24只SD大鼠随机分成4组,为正常大鼠组、假手术组、CCD 3 d组、7 d组。检测大鼠脊髓HMGB1 mRNA的表达情况。(2)24只SD大鼠分成4组,行CCD手术。术后7 d鞘内给予生理盐水、HMGB1的中和抗体10、30、100μg,检测大鼠各时间点机械性缩足阈值。(3)24只SD大鼠分成4组(n=6),鞘内给予生理盐水、HMGB1的中和抗体10、30、100μg,检测大鼠的运动功能。(4)30只SD大鼠分成5组(n=6)。在CCD术后7 d鞘内给予saline、HMGB1的中和抗体10、30、100μg,检测大鼠脊髓TNF-α、IL-1β和IL-6 mRNA的表达。结果:(1)CCD术后3 d和7 d,脊髓内HMGB1 mRNA的表达明显上调(P<0.05)。(2)鞘内给予HMGB1的中和抗体30、100μg后可以明显逆转CCD大鼠术后7 d的机械性痛敏,且其作用可以持续24 h(P<0.05)。(3)鞘内给予HMGB1的中和抗体没有引起大鼠的运动功能损伤(P>0.05)。(4)鞘内给予HMGB1的中和抗体30、100μg可以显著抑制CCD大鼠术后7 d组脊髓内的TNF-α、IL-1β、IL-6 mRNA的表达(P<0.05)。结论:脊髓内HMGB1的上调可能参与了CCD大鼠痛敏状态的形成。Objective： To observe the dange of high-mobility group box 1 （HMGB1） in the spinal cord in a rat model of chronic compression of dorsal root ganglion （CCD） , to explore its mechanism in pain transmission, and to provide new targets for the treatment of chronic pain. Methods ： （ 1 ） 24 SD rats were randomly divided into four groups （ n = 6） ： normal group, sham group, CCD 3 d group, CCD 7 d group. The expression of HMGB1 mRNA in spinal dorsal horn was detected. （2） 24 SD rats were randomly divided into four groups （ n = 6） and CCD operation was performed on all the rats. Seven days after surgery, saline or neutralizing antibody of HMGB1 （10, 30 or 100 μg） were intrathecally administrated to investigate the effect of HMGB1 on paw withdrawal threshold of the CCD rat. （ 3 ） 24 SD rats were randomly divided into four groups （n = 6 ）. Saline or neutralizing antibodies of HMGB1 （10, 30 or 100 μg） were intrathecally given to detect the effect of H.MGB1 on motor function in normal rats. （4） 30 SD rats were randomly divided into five groups （n = 6 ）. One group was as normal group without any treatment. The remaining four groups were performed on the CCD operation and were intrathecally given saline or neutralizing antibody of HMGB1 （ 10, 30 or 100 μg） to observe the mRNA expression of TNF-α, IL-1β and IL-6 in spinal dorsal horn. Results： （1） The expression of HMGB1 mRNA in the spinal cord was significantly increased on 3 d and 7 d after CCD surgery （ P 〈 O. 05 ）. （2） Intrathecal neutralizing antibody of HMGB1 （30 or 100 μg） could significantly reverse the mechanical hyperalgesia on 7 d after CCD surgery, and its effect lasted up to 24 h （P 〈0.05）. （3） Intrathecally administration of neutralizing antibody of HMGB1 （ 10, 30 or 100 μg） didn＇t cause motor disfunction in rats （P 〉 0.05 ）. （4） Intrathecally delivery of neutralizing antibody of HMGB1 （30 or 100 μg） could significantly inhibit the mRNA expression of

关 键 词：神经病理性痛 高迁移率蛋白-1 HMGB1 脊髓 细胞因子 大鼠 

分 类 号：R338[医药卫生—人体生理学]