右美托咪定对神经病理性痛大鼠脊髓背根神经节神经元c-fos蛋白表达的影响

Effect of dexmedetomidine on expression of c-fos protein in dorsal root ganglion neurons in a rat model of neuropathic pain

目的 评价右美托咪定对神经病理性痛大鼠脊髓背根神经节神经元c-fos蛋白表达的影响.方法 清洁级健康成年雄性SD大鼠72只,体重180～ 240 g,采用随机数字表法分为3组（n=24）：假手术组（S组）仅分离坐骨神经但不结扎;神经病理性痛组（NP组）采用结扎坐骨神经的方法制备大鼠神经病理性痛模型;右美托咪定组（Dex组）于结扎坐骨神经后至处死每天腹腔注射右美托咪定50μg/kg,S组和NP组注射等容量生理盐水.于结扎前1 d（To）、结扎后3、7和14 d（T1-3）时测定大鼠机械缩足反应阈（MWT）和热缩足潜伏期（TWL）;于T1-3时测定痛阈后各组随机取8只大鼠处死,取L45脊髓背根神经节,采用免疫组化法检测神经元c-fos蛋白的表达.结果 与S组比较,NP组和Dex组T1-3时MWT降低,TWL缩短,脊髓背根神经节神经元c-fos蛋白表达上调（P＜0.05）;与NP组比较,Dex组T1-3时MWT升高,TWL延长,脊髓背根神经节神经元c-fos蛋白表达下调（P＜0.05）.结论 右美托咪定可通过抑制脊髓背根神经节神经元c-fos蛋白表达上调减轻大鼠神经病理性痛.

Objective To evaluate the effect of dexmedetomidine on the expression of c-fos protein in the dorsal root ganglion neurons in a rat model of neuropathic pain （NP）.Methods Seventy-two adult male SpragueDawley rats,weighing 180-240 g,were randomly divided into 3 groups （n =24 each） using a random number table：sham operation group （group S）,group NP,and dexmedetomidine group （group Dex）.The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The right sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread in NP and Dex groups.In group Dex,dexmedetomidine 50μg/kg was injected intraperitoneally once a day starting from the end of operation until the animals were sacrificed.The equal volume of normal saline was given instead of dexmedetomidine in S and NP groups.The mechanical paw withdrawal threshold （MWT） and thermal paw withdrawal latency （TWL） were measured at 1 day before ligation （T0,baseline） and 3,7 and 14 days after ligation （T1-3）.Eight animals were sacrificed after measurement of pain threshold at T13 and the dorsal root ganglions of the lumbar segments （L44） were removed for detection of c-fos expression （by immuno-histochemistry）.Results Compared with group S,MWT was significantly decreased,TWL was shortened,and the expression of c-fos protein was up-regulated at T1-3 in NP and Dex groups.Compared with NP group,MWT was significantly increased,TWL was prolonged,and the expression of c-fos protein was down-regulated at T1-3 in Dex group.Conclusion Dexmedetomidine can inhibit upregulation of c-fos protein expression,thus attenuating NP in rats.