糖皮质激素对坐骨神经分支选择性损伤大鼠神经病理性疼痛的影响

The Effect of Glucocorticoid on the Neuropathic Pain of the Rat Spare Nerve Injury Model

目的观察糖皮质激素对大鼠坐骨神经分支选择性损伤(SNI)所致神经病理性疼痛的影响。方法将80只雄性SD大鼠随机分4组:假手术组(Sh);模型组(S);鞘内注射得宝松组(D1)及局部注射得宝松组(D2)。其中S组和D1组术后分别单次鞘内注射盐水20μl和得宝松20μ(l2μg/μl);D2组术后单次鞘内注射盐水20μl,同时于神经损伤的局部单次注射得宝松1 ml(1 mg/ml)。记录全组动物术前1 d及术后1,3,7,14 d的机械缩足反射阈值(MWT)和热缩足反射维持时间(TWD),并在术后各时点用免疫组化法检测星形胶质细胞酸性纤维蛋白(GFAP)和糖皮质激素受体(GR)的表达,同时用免疫印迹法检测GR蛋白量的变化,用ELISA法检测TNF-α和IL-1β含量的变化。结果S组术后出现明显的MWT下降和TWD延长,与术前及Sh组术后各时点比较差异显著(P<0.01),与S和D1组比较D2组行为学指标的变化幅度小(P<0.05)。S组GFAP、GR及TNF-α和IL-1β的含量术后均增加,与Sh组比较差异显著(P<0.01);D1和D2组GFAP及TNF-α和IL-1β的含量升高的幅度小,与S组比较有统计学差异(P<0.05);D2组GR的表达量升高最明显,与S和D1组比较有统计学差异(P<0.05)。结论糖皮质激素能抑制SNI大鼠脊髓星形胶质细胞的激活和炎性介质的释放;局部使用激素对脊髓内GR的影响小,且能改善SNI大鼠神经病理性疼痛。

Objective To investigate the effect of glucocorticoid on the neuropathic pain of the rat spare nerve injury（SNI）model.Methods Eighty male SD rats were randomly divided into four groups ：GroupⅠ,sham operation（Sh）;Group Ⅱ,SNI model（S）in which the rats underwent SNI and were intrathecally injected with normal saline 20 μl;Group Ⅲ intrathecal betamethasone（Diprospan） group（D1） in which the rats received SIN with intrathecal injection of Diprospan 20 μl（2 μg/μl）;Group Ⅳ local Diprospan group（D2）in which the SIN model rats were locally injected by Diprospan 1 ml （ 1 mg/nd）. Mechanical withdraw threshold （MWT） and thermal withdraw duration （TWD） of the rats were measured with Von Frey hair or Hargreaves tests on pro-operative day 1 and postoperative day 1,3,7, 14. We assessed the expression of glial fibrillary acid protein （GFAP） and glucocorticoid receptors （GRs） by inmlunohistochemistry, and TNF-α and IL-1βlevels by ELISA on postopteration. We also examined GRs expression by Western blot. Results After operation, the SNI rats displayed marked mechanical allodynia and thermal hyperalgesia even treated by glucocorticoid. However,local injection of glucocoaicoid caused a sig- nificant reduction of mechanical allodynia and thermal hyperalgesia, compared with intrathecal injection. Spared nerve injury caused significant activation of GFAP,GRs and TNF-α and IL-1β after operation. Treatment of glucocorticoid by two different ways could suppress the activation of GFAP and the elevation of TNF-α and IL-1β. Inwathecal injection of glucocorticoid would result in much more significant activation of spinal GRs than local administration. Conclusion Glucocorticoid given by both approaches could suppress the activation of GFAP and the elevation of TNF-α and IL-1β. Local injection of glucocorticoid had relatively slight influence on spinal GRs and displayed to attenuate the development of mechanical allodynia and thermal hyperalgesia.