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2011年第10期
磷酸化ERK1、2参与雌激素对切口痛大鼠的伤害性感受调节
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DOI:
作者:
姚婧鑫,?赵欣,薛庆生,于布为
YAO Jingxin, ZHAO Xin, XUE Qingsheng,YU Buwei
作者单位:
上海交通大学附属瑞金医院麻醉科
Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine
关键词:
雌激素;切口痛;胞外信号调节激酶1/2;伤害性感受
estrogen;incision pain;ERK1/2;nociception
摘要:
目的 通过大鼠切口痛模型来探讨磷酸化胞外信号调节激酶1/2 (phosphorylation extracellular signal-regulated kinases,pERK1/2)参与雌激素对伤害性感受调节的作用机理。方法 成年SD雌鼠32只,在卵巢切除术(ovariectomy,OVX)后第15 d建立切口痛模型,将其大鼠随机分四组,每组8只:雌激素替代(50μg雌二醇溶于100μl橄榄油)+切口痛假手术组(E+S组);溶剂替代(100μl橄榄油)+切口痛假手术组(V+S组);雌激素替代(50μg雌二醇溶于100μl橄榄油)+切口痛组(E+I组);V+I组:溶剂替代(100μl橄榄油)+切口痛组(V+I组)。OVX术后14 d起每两天行腹腔注射雌激素一次至完成行为学实验,对照组注射等体积橄榄油。于OVX术前、切口痛术前和假手术术前当天及术后(OVX术后15 d)第1、3、5、7 d(即OVX术后第16、18、20、22 d)进行热痛实验,记录热缩足潜伏期(PWTL)。完成行为学实验后,使用免疫印迹法检测大鼠脊髓背角pERK1/2。 结果 OVX术后16、18、20、22 d,V+S组较E+S组PWTL显著延长(P﹤0.05),切口痛术后E+I、V+I组大鼠的PWTL较术前显著缩短,切口痛术后第1、3 d,E+I组的PWTL显著低于V+I组(P﹤0.05),E+I组PWTL值于术后第5 d恢复切口痛术前水平,V+I组于术后第7 d恢复。雌激素替代组较溶剂替代组pERK1/2水平显著增加(P<0.05),切口痛组手术侧pERK1/2水平较非手术侧显著增加(P<0.05)。结论 雌激素替代增加了雌性去势大鼠切口痛术后对伤害性热刺激的敏感度;pERK1/2参与了雌激素对伤害性刺激感受的调节作用。
Objective: To investigate the role of pERK1/2 (phosphorylation extracellular signal-regulated kinases) in the mechanisms of estrogen modulative effects on the nociception of incision pain rats. Methods: Thirty two adult ovariectomized (OVX) female rats were used for this study. Estrogen or vehicle replacements were performed every other day during the period from 14 days after OVX to the end of pain behavior test. The plantar incision operation was performed on the 15th day after OVX. OVX rats were divided into four groups, with 8 rats in each group. Group E+S: Estrogen replacement (50 μg) + sham incision, group V+S: vehicle replacement (100 μl Oliver) + sham incision. Group E+I: estrogen replacement + incision operation, group V+I: vehicle replacement + incision operation. Paw withdrawal thermal latency (PWTL) assessment as the pain behavior test was used before OVX, 2 day before paw incision operation, and, 1, 3, 5, 7 days after incision. The ERK1/2 phosphorylation (pERK1/2) in spinal dorsal cord was assayed after the pain behavior test. Results:The PWTL of rats in group V+S at 16, 18, 20, 22 day after OVX were significantly increased as compared with the PWTL in group E+S (P<0.05). The PWTL of rats in group E+I and group V+I at 1 and 3 days after incision operation were significant lower than the PWTL before incision of themselves. The PWTL of rats in group E+I were significantly reduced when compared with the PWTL of group V+I at 1 and 3 days after incision operation. The PWTL of rats in group E+I and group V+I were reverted to the levels of before incision operation at 5 days and 7 days after operation, respectively. The pERK1/2 expression in the spinal cord of rats in estrogen replacement groups were augmented more than those in the vehicle groups. After incision operation, the level of pERK1/2 in the ipsilateral was higher than that in the contralateral of rat’s spinal cord. Conclusions: Estrogen can increase the nociception of OVX incision pain rats, and pERK1/2 in their spinal cord may participate in its mechanisms.