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目的:观察鞘内注射P2Y13受体阻断剂MRS2211对糖尿病神经病理性疼痛大鼠机械痛阈及脊髓背角Iba-1和IL-6表达变化的影响。方法:成年SD大鼠随机分为4组(n=8):正常组(仅鞘内注射生理盐水)、药物+正常大鼠组(鞘内注射MRS2211 100 pmol/L)、糖尿病大鼠模型组(diabetes mellitus,DM组)、MRS2211处理组(糖尿病大鼠+鞘内注射MRS2211 100 pmol/L)。SD大鼠单次腹腔注射链脲菌素60 mg/kg,2周后机械痛阈下降认为造模成功。各组大鼠开始鞘内注射生理盐水或MRS2211(100 pmol/L)每周二次,连续4周。在STZ注射前1 d、注射后第2,4,6周末测定给药后机械缩足反射阈值(mechanical withdrawl threshold,MWT);免疫印迹观察STZ注射后2、4、6周末大鼠脊髓背角Iba-1和IL-6表达变化。结果:与正常组相比,DM组MWT明显降低(P<0.01),第2、4、6周末背角Iba-1和IL-6表达也明显上调(P<0.01)。与DM组4周相比,MRS2211处理组MWT明显提高(P<0.01);与DM组6周相比,MRS2211处理组MWT没有明显变化。与DM组4周相比,MRS2211处理组明显抑制STZ注射4周时脊髓背角Iba-1和IL-6表达上调(P<0.01);但与DM组6周相比,MRS2211处理组在STZ注射6周时Iba-1和IL-6表达没有明显变化。结论:鞘内注射P2Y13受体拮抗剂MRS2211可以明显抑制糖尿病大鼠早期的机械痛敏症状,同时脊髓背角Iba-1表达和IL-6表达上调明显减弱。MRS2211有可能通过影响脊髓背角小胶质细胞功能在脊髓水平发挥镇痛作用。
Objective: To observe the effects of intrathecal injection of P2Y13 receptor antagonist MRS2211 on mechanical pain threshold and expression of Iba-1 and IL-6 in dorsal horn of diabetic neuropathic pain rats. Methods: Adult SD rats were randomly divided into 4 groups (n = 8): normal group (intrathecal saline only), drug + normal group (intrathecal MRS2211 100 pmol / L), diabetic rat model group (diabetes mellitus, DM group) and MRS2211 treatment group (diabetic rat + intrathecal MRS2211 100 pmol / L). SD rat single intraperitoneal injection of streptozotocin 60 mg / kg, 2 weeks after the mechanical pain threshold decreased as modeling success. Rats in each group started intrathecal injection of saline or MRS2211 (100 pmol / L) twice a week for 4 weeks. The mechanical withdrawl threshold (MWT) was measured at the end of the second, fourth and sixth week after injection, and the spinal cord dorsal horn Iba-1 and IL-6 expression changes. Results: The MWT of DM group was significantly lower than that of the normal group (P <0.01), and the expressions of Iba-1 and IL-6 at the 2nd, 4th, 6th week were also significantly increased (P <0.01). MWT of MRS2211 group was significantly higher than that of DM group (P <0.01). Compared with DM group, MWT of MRS2211 group did not change significantly compared with DM group. MRS2211 treatment significantly inhibited the up-regulation of Iba-1 and IL-6 in spinal dorsal horn (P <0.01) at 4 weeks after STZ injection compared with those in DM group at 4 weeks. However, compared with DM at 6 weeks, There was no significant change in the expression of Iba-1 and IL-6 at 6 weeks after injection. Conclusion: Intrathecal injection of P2Y13 receptor antagonist MRS2211 can significantly inhibit the early mechanical hyperalgesia symptoms in diabetic rats. In addition, Iba-1 expression and IL-6 upregulation in spinal dorsal horn were significantly reduced. MRS2211 may exert analgesic action at spinal level by affecting microglia function in spinal dorsal horn.