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目的:评估帕瑞昔布钠及甲基强的松龙对慢性坐骨神经挤压损伤(CCI)模型大鼠神经病理性疼痛的影响。方法:将40只180~220 g成年雄性SD大鼠随机分为假手术组、手术对照组、帕瑞昔布纳组、甲基强的松组、帕瑞昔布纳+甲基强的松组,每组各8只。从术后3 d开始,帕瑞昔布纳组予帕瑞昔布钠10 mg/kg腹腔注射;甲基强的松组予甲基强的松30 mg/kg腹腔注射;帕瑞昔布纳+甲基强的松组予帕瑞昔布钠10 mg/kg+甲基强的松30 mg/kg腹腔注射;假手术组、手术对照组给予生理盐水1 mL腹腔注射。分别于术前1(1和术后1、3、5、7、10、14 d测定机械刺激痛域(MWT)。术后14 d处死大鼠,取脊髓腰膨大段背角组织,Western Blotting法检测TNF-α、IL-1β和NF-κB的表达。结果:隙假手术组外,其余各组大鼠MWT从术后3 d开始明显升高(P<0.05)。术后14 d,帕瑞昔布纳+甲基强的松组MWT基本恢复正常,与假手术组比较,差异无统计学意义(P>0.05);帕瑞昔布纳组、甲基强的松组、帕瑞昔布纳+甲基强的松组MWT较手术对照组明显升高(P<0.05),帕瑞昔布纳+甲基强的松组MWT高于帕瑞昔布纳组、甲基强的松组(P<0.05),帕瑞昔布纳组MWT高于甲基强的松组(P<0.05)。手术对照组TNF-α和NF-κB表达水平明显高于其余各组(P<0.05);帕瑞昔布纳+甲基强的松组TNF-α和NF-κB表达水平明显低于帕瑞昔布纳组、甲基强的松组(P<0.05);与假手术组比较,则差异无统计学意义(p>0.05);帕瑞昔布纳组、甲基强的松组TNF-α和NF-κB表达水平明显高于假手术组(P<0.05):帕瑞昔布纳组TNF-α和NF-κB表达水平明显低于甲基强的松组(P<0.05)。各组IL-1β表达水平比较,差异均无统计学意义(P>0.05)。结论:帕瑞昔布钠及甲基强的松龙能减轻大鼠神经病理性疼痛,两药合用能缓解大鼠的神经病理性疼痛。其机制可能是抑制脊髓背角的NF-κB的激活及其下游炎性因子TNF-α释放有关。
Objective: To evaluate the effect of parecoxib sodium and methylprednisolone on neuropathic pain in chronic constriction injury (CCI) rats. Methods: Forty adult male Sprague Dawley rats (180-220 g) were randomly divided into sham operation group, operation control group, parecoxib group, methylprednisolone group, parecoxib + methylprednisone Group, each group of 8. From the 3rd day after operation, parecoxib group was given intraperitoneal injection of parecoxib 10 mg / kg; methyl prednisone 30 mg / kg methylprednisone intraperitoneal injection; + Methyl prednisone group to parecoxib sodium 10 mg / kg + methyl prednisone 30 mg / kg intraperitoneal injection; sham operation group, the control group were given saline 1 mL intraperitoneal injection. Rats were sacrificed 14 days after operation and the lumbar dorsal horn of lumbar spinal cord was harvested at 1 and 1, 3, 5, 7, 10 and 14 days before operation, respectively. Western Blotting And the expression of TNF-α, IL-1βand NF-κB were detected by immunohistochemistry.Results: The MWT of rats in other groups were significantly increased from 3 days after operation (P <0.05) There was no significant difference in the MWT between Parecibeno and Methylprednisolone group (P> 0.05). Parecoxib group, Methylprednisolone group and Pary The MWTs in both Cibonone and Methylprednisolone groups were significantly higher than those in the control group (P <0.05). The MWTs in parecoxib + methylprednisolone group were higher than those in parecoxib group (P <0.05), and the MWT in Parecoxib group was higher than that in methylprednisolone group (P <0.05) .The expression of TNF-α and NF-κB in the operation control group was significantly higher than that in other groups (P < 0.05). The expressions of TNF-α and NF-κB in parecoxib + methylprednisolone group were significantly lower than those in parecoxib group and methylprednisolone group (P <0.05) (P> 0.05). The expression of TNF-α and NF-κB in parecoxib group and methylprednisolone group were significantly lower than those in control group (P <0.05): The expression of TNF-α and NF-κB in Parecoxib group was significantly lower than that in methylprednisolone group (P <0.05) .Compared with the sham-operated group (P> 0.05) .Conclusion: Parecoxib sodium and methylprednisolone can reduce the neuropathic pain in rats and the combination of the two drugs can relieve the neuropathic pain in rats.The mechanism may be Is to inhibit the spinal dorsal horn of NF-κB activation and its downstream inflammatory cytokine TNF-α release.