右美托咪啶对神经痛大鼠脊髓背角pERK、pCREB表达的影响

Effection of Dexmedet Tomidine on Expression of pERK, pCREB in Spinal Cord Dorsal Horn in a Rat Model of Chronic Neuropathic Pain

目的：评价右美托咪啶对神经病理性痛大鼠脊髓背角神经元磷酸化胞外反应激酶（phosphoryltion of extracellular regulated proteinkinases，pERK）、磷酸化cAMP反应元件结合蛋白（phosphoryltion of Camp response element bound protein，pCREB）蛋白表达的影响。方法：健康成年雄性Wistar大鼠54只，6～8周龄，体重180-220g，采用随机数字表法，将其分为3组（Il=18）：假手术组（s组）、慢性神经病理性痛组（C组）和右美托咪啶组（D组）。S组仅分离坐骨神经但不结扎，C组和D组采用结扎坐骨神经的方法制备大鼠坐骨神经慢性压迫性损伤（chronicconstriction injury，CCI）的神经病理性痛模型，D组于术后即刻开始至处死前1d腹腔注射右美托咪啶50μg／kg，1次，d，s组和C组注射等容量生理盐水。于术前1d、术后3、7、14d时以缩足阈值（pawwithdrawal threshold，P、ⅣT）测定大鼠机械痛阈和辐射热的缩足潜伏期（pawwithdrawl latency，PWL）测定大鼠的热痛阈，并于术后测定痛阈后灌注处死大鼠，取L4．6脊髓组织，采用免疫组织化学法检测脊髓背角神经元pERK、pCREB的表达水平。结果：与s组比较，c组和D组术后3、7、14d时MWT降低，TWL缩短，脊髓背角pERK、pCREB表达上调（P〈0．05）；与c组比较，D组术后3、7、14d时MWT升高，T、TWL延长，脊髓背角pERK、pCREB表达下调（P〈0．05）。与术前1d比较，c组和D组术后3、7、14d时MWT降低，TWL缩短：与术后3d时比较。C组和D组7、14d时MWT降低，TwL缩短，脊髓背角pERK、pCREB表达上调（P〈0．05）。结论：右关托咪啶可减轻大鼠慢性神经病理性痛，抑制pERK、pCREB的表达可能是其作用机制之一。

Objective： To investigate the effects of dexmedetomidine （Dex） on the expression levels of pERK,pCREB in spinal dorsal hom in a rat model of chronic neuropathic pain （CNP）. Methods： Fifty-four adult male wistar rats weighing 180-220 g were randomly divided into 3 groups （n =18）： sham operation group （group S）, chronic constriction injury group （group C） and dexmedetomidine group （group D）. The animals were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg. Four ligatures were placed on right sciatic nerve at 1 mm intervals with 4-0 silk thread in group C and group D. In group D, Dex 50 μg/kg was injected intraperitoneally （IP） once a day starting from the end of operation until the animals were sacrificed. 50 % paw withdrawal threshold （PWT） to mechanical stimulation with yon Frey filament and paw withdrawal latency to thermal stimulation （TWL） were measured on the preoperative day and the 3rd, 7th and 14th day after operation. Animals of three groups were killed at each time points after the measurement of PWT and TWL. Their lumbar segments （L4-6） were removed for measuring the expression of pERK, pCREB by immunohistochemistry. Results： CCI significantly decreased PWT and PWL, increased the expression of pERK, pCREB on the 3rd, 7th and 14th day in spinal dorsal horn in group C and group D compared with group S. Intraperitoneal injection Dex significantly attenuated CCl-induced mechanical and thermal hyperalgesia in group D as compared with group C. Intraperitoneal injection of Dex further decreased pERK, pCREB expression in group D compared with group C. Conclusion： Intraperitoneal injection DEX can reduce the chronic neuropathic pain in rats, the mechanism may probably related to inhibition the expression of pERK, pCREB in spinal dorsal horn.