槲皮素抑制脊髓小胶质细胞基质金属蛋白酶的表达改善术后疼痛的机制研究

考察槲皮素对足底切口诱发的术后疼痛的影响，并探讨其对脊髓小胶质细胞中基质金属蛋白酶(MMP)-9和MMP-2的抑制作用并考察其作用机制。制备小鼠足底切口术后痛模型，利用Von Frey Hairs检测小鼠机械痛阈值；利用明胶酶谱法检测槲皮素对脊髓水平MMP-9和MMP-2活力的影响；Western blot法检测小鼠脊髓小胶质细胞标记分子钙离子结合蛋白1(IBA-1)以及磷酸化p38丝裂原活化蛋白激酶(p-p38 MAPK)的变化。结果发现，给予槲皮素(20，40，80 mg/kg，ip)能够显著地抑制足底切口手术引起的机械性痛觉异常以及脊髓小胶质细胞中MMP-9和MMP-2水平的升高；并抑制术后切口引起的脊髓水平IBA-1和p-p38的表达。研究结果表明，槲皮素可能通过抑制脊髓小胶质细胞中MMP-9和MMP-2的活化而改善术后疼痛。

Quercetin ameliorates postoperative pain by suppressing matrix metalloproteinase in microglia

The aim of the present study was to investigate the effects and mechanisms of quercetin on plantar incision-induced matrix metalloproteinase(MMP)-9 and MMP-2 activity, microglia activation and the analgesic effect of quercetin on plantar incision surgery-treated mice. Postoperative pain model was mediated by plantar incision surgery and Von Frey Hairs was used to test the mechanical pain threshold. The activity of MMP-9 and MMP-2 in spinal cord was evaluated by gelatin zymography. The marker of microglia ionized calcium binding adapter molecule 1(IBA-1), phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK)was detected by Western blot. Results showed that quercetin(20, 40, 80 mg/kg, ip)significantly inhibited plantar incision-induced mechanical allodynia and suppressed the activity of MMP-9 and MMP-2 in the spinal cord. Moreover, quercetin also markedly inhibited plantar incision-induced up-regulation of IBA-1 and p-p38 in spinal cord. In conclusion, quercetin may alleviate postoperative pain by suppressing MMP-9 and MMP-2 activity in microglia.