帕瑞昔布钠对神经病理性疼痛大鼠脊髓背角胶质纤维酸性蛋白及脊髓炎性反应的影响

Effects of Parecoxib on the Expression of GFAP in Spinal Dorsal Horns and Inflammatory Responses in Spinal Cord of Rats with Neuropathic Pain

目的评价帕瑞昔布钠对神经病理性疼痛大鼠脊髓背角胶质纤维酸性蛋白(GFAP)及脊髓炎性反应的影响。方法成年雄性SD大鼠42只,体重250~300 g,采用随机数字表法分为3组(n=14):假手术组(S组)、神经病理性痛组(CCI组)、帕瑞昔布钠组(P组)。CCI组和P组采用坐骨神经慢性压榨性损伤(CCI)法制备大鼠神经病理性疼痛模型;S组仅分离坐骨神经但不结扎;P组在术后经鼠尾静脉注射帕瑞昔布钠10 mg/(kg·d),连续3 d;S组、CCI组在相同时点经尾静脉注射等容量的生理盐水。于术前1 d、术后4、7、14 d测定热痛阈、机械痛阈。于术后14 d测定热痛阈和机械痛阈1 h后取L4-6脊髓组织,采用免疫组化SP法测定脊髓背角胶质纤维酸性蛋白表达;ELISA法检测脊髓中环氧合酶-2(COX-2)、白细胞介素1β(IL-1β)及肿瘤坏死因子α(TNF-α)含量。结果与S组比较,CCI组和P组术后4 d、7 d、14 d时热痛阈、机械痛阈明显缩短(P<0.05),术后14 d时脊髓背角GFAP表达明显增加(P<0.05),脊髓中COX-2、IL-1β及TNF-α含量升高(P<0.05)。与CCI组比较,P组术后4 d、7 d、14 d时热痛阈、机械痛阈明显升高(P<0.05),术后14 d时脊髓背角GFAP表达明显减少(P<0.05),脊髓中COX-2、IL-1β及TNF-α含量降低(P<0.05)。结论帕瑞昔布钠可减轻大鼠神经病理性疼痛,其机制与抑制脊髓背角星形胶质细胞激活,减少COX-2表达、减少脊髓中炎症介质IL-1β、TNF-α有关。

Objective To investigate the effects of parecoxib on the expression of GFAP in spinal dorsal horns and inflammatory responses in spinal cord of rats with neuropathic pain.Methods Fourty-two male SD rats,weighting 250-300 g,were randomly divided into 3 group(n=14):sham operation group(group S),group CCI and group P.The rats in group S had their sciatic nerve exposed without ligation.Rats in group CCI and group P underwent sciatic nerve ligation to induce neuropathic pain.The rats in group P were injected with parecoxib sodium 10 mg/(kg·d)through the tail vein for 3 days after operation.In group S and group CCI,the rats were injected with 0.9%NS through the tail vein at the same time.On 1 day before surgery and 4,7,14 days after surgery,the mechanical paw with drawal threshold(MWT)and thermal paw withdrawal latency(TWL)were measured.The rats were sacrificed at the 14st after surgery;L4-6 segments of the spinal cords were removed.The expression of glial fibrillary acidic protein(GFAP)was detected by immunohistochemistry.The levels of cyclooxygenase-2(COX-2),interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)were detected by ELISA.Results Compared with group S,the MWT and TWL of group CCI and group P were significantly shortened(P<0.05)on 4d,7d and 14d after operation,and GFAP expression of spinal dorsal horn increased significantly at 14d after operation(P<0.05).The levels of COX-2,IL-1β and TNF-α in the spinal cord increased(P<0.05).Compared with group CCI,the MWT and TWL of group P were significantly extended(P<0.05)on 4d,7d and 14d after operation,and GFAP expression of spinal dorsal horn increased significantly on 14d after operation(P<0.05).The levels of COX-2,IL-1β and TNF-αin the spinal cord decreased(P<0.05).Conclusion Parecoxib sodium can reduce the neuropathic pain in rats through inhibiting the spinal dorsal horn astrocyte activation,reducing COX-2 expression and reducing the inflammatory mediators of IL-1β,TNF-α in spinal cord.