右美托咪定对神经病理性疼痛大鼠脊髓P2X4R蛋白表达的影响

EFFECTS OF DEXMEDETOMIDINE ON P2X4R PROTEIN EXPRESSION IN SPINAL CORD OF NEUROPATHIC PAIN RATS

目的：观察右美托咪定对神经病理性痛大鼠脊髓P2X4R总蛋白及膜蛋白表达水平的影响。方法：雄性SD大鼠40只,180~220 g,随机分为4组（每组10只）：正常组（N组）、假手术组（S组）、神经病理性痛组（SNI组）、右美托咪定组（Dex组）。N组不作任何处理,Dex组于术后即刻腹腔注射右美托咪定40μg/kg,间隔24 h追加给药一次至术后14 d,S组和SNI组均腹腔注射等容量的生理盐水。术前1 d及术后1、3、5、7、14 d检测机械缩足反射阈值（MWT）。术后14 d用Western blot方法检测脊髓L4~6节段P2X4R总蛋白和膜蛋白表达量。结果：与N组和S组相比,SNI组大鼠术后MWT明显降低（P〈0.05）,脊髓水平P2X4R总蛋白和膜蛋白表达量均明显增加（P〈0.05）;与SNI组相比,Dex组MWT明显升高（P〈0.05）,脊髓水平P2X4R总蛋白和膜蛋白表达量均明显降低（P〈0.05）。结论：Dex能减轻大鼠神经病理性痛,其机制可能与抑制脊髓P2X4R总蛋白及膜蛋白水平有关。

Objective： To investigate effects of dexmedetomidine on neuropathic pain （ NP ） and expression of P2X4R protein in the spinal cord in rats with NP. Methods： Forty male SD rats weighing 180 - 220 g were randomly divided into 4 groups （ n = 10 in each group ） , they were naive （ N ） , sham-operated （S）, neuropathic pain （ SNI ） and dexmedetomidine-treated groups （ Dex ） respectively. N group rats received no treatment. In Dex group, Dexmedetomidine （ 40 lag/kg） was injected intraperitionally daily for 14 days starting immediately after surgery. S and SNI groups rats were injected saline as control. The mechanical paw withdrawal threshold （ MWT ） were measured before surgery and on postoperative day 1, 3, 5, 7 and 14. The L4-6 segment of spinal cords were used to determinate the level of P2X4R total protein and membrane protein by Western blot on day 14. Results： MWT were significantly decreased （P 〈 0.05） and the level of expression of P2X4R total protein and membrane protein increased significantly in the spinal cord in SNI rats, compared with those in N group and S group （ P 〈 0.05 ） . Compared with SNI group, MWT were significantly increased and the expression of P2X4R total protein and membrane protein were significantly down-regulated after operation in Dex group （ P 〈 0.05 ） . Conclusion： Dexmedetomidine can reduce neuropathic pain in rats with SNI and its underlying mechanism may be involved in inhibition of expression of P2X4R.