右美托咪定对脊神经结扎大鼠脊髓背角高迁移率族蛋白B1的影响

Effect of dexmedetomidine on high mobility group box 1 protein expression in the spinal dorsal horn of rats underwent spinal nerve ligation

目的观察右美托咪定（dexmedetomidine，DEX）对脊神经结扎大鼠机械痛阈和热痛阈的作用及对脊髓背角高迁移率族蛋白B1（high mobility group box 1 protein，HMGB1）的影响。方法雄性SD大鼠30只，采用随机数字表法随机分为3组：假手术组（Sham组）、脊神经结扎组（SNL组）和DEX处理组，每组10只。各组大鼠经L4-5鞘内置管后，SNL组和DEX组大鼠行左侧L5脊神经结扎术。DEX组于术后鞘内注射DEX2μg／10μl，Sham组和SNL组注射等容生理盐水，每日1次，连续7d。观察各组大鼠行为学变化。7d后处死大鼠，Western blot法检测大鼠左侧L。脊髓背角HMGBl表达。结果SNL组大鼠左后肢缩足反应阈值（paw withdrawal threshold，PWT）和缩足潜伏期（paw withdrawal latency，PWL）在术后第1天和第3天开始分别明显降低，且持续到术后第7天（P〈0．05）。术后第7天PWT、PWL分别为（12．9±1．6）g和（8．3±0．9）s，与Sham组比较分别降低67％和41％（P〈0．05），而脊髓背角HMGB1表达增高84％（P〈0．05）；与SNL组比较，DEX组大鼠相应时间点PWT和PWL明显增高（P〈0．05）。术后第7天PWT、PWL分别为（22．3±3．2）g和（10．4±1．1）s，较SNL组分别升高73％和25％（P〈0．05），而脊髓背角HMGB1表达降低29％（P〈0．05）。结论脊髓背角HMGB1表达增高参与了SNL诱导的神经病理痛；鞘内注射DEX能明显缓解SNL诱导的神经病理痛，其镇痛作用可能与抑制大鼠脊髓背角HMGB1水平有关。

Objective To investigate the effect of dexmedetomidine （DEX） on high mobility group box 1 protein （HMGB1） expression in the L4-5 dorsal horns of rats underwent spinal nerve ligation. Methods Thirty male SD rats were randomly divided into three groups（n=10）： sham operation group（Sham group）, L5 spinal nerve ligation group（SNL group） and DEX -treatment group（DEX group）. After intratheeal catheter implantation between L-5 vertebrae, the rats in SNL group and DEX group were underwent L5 spinal nerve ligation. The surgical procedure for the the rats in Sham group was identical except nerve ligation. Then DEX （2 μg/10μL） was injected intrathecally via intrathecal catheter in the rats of DEX group after L5 spinal nerve ligation, the same volume of normal saline was injected intraperitoneally in rats of Sham group and SNL group. Expression of HMGB1 in the spinal dorsal horn was measured by Western blot. Results Compared to Sham group, the paw withdrawal threshold（PWT） and paw withdrawal latency （PWL） of rats in SNL group were significantly decreased from 1 d and 3 d after SNL, respectively, and lasted for 7 d （P〈0.05）. On day 7 after SNL, the PWT（12.9±1.6） g and PWL（8.3±0.9） s were decreased 67% and 41%, respectively（P〈0.05）, with the levels of HMGB1 expression increased 84%（P〈0.05）. Compared to SNL group, the PWT and PWL of rats in DEX group were significantly increased （P〈0.05）. On day 7 after SNL, the PWT（22.3±3.2） g and PWL（ 10.4±1.1 ） s were increased 73% and 25%, respectively（P〈0.05）, with the levels of HMGB1 expression decreased 29%（P〈0.05 ）. Conclusions Increase of HMGB1 expression in spinal dorsal horn was involved in SNL-induced neuropathic pain. DEX injected intrathecally ameliorated SNL-induced mechanical allodynia and thermal hyperalgesia, the effect may be related to inhibition of HMGB1 expression by DEX.