钙蛋白酶1在瑞芬太尼诱发大鼠疼痛过敏中的作用

doi:10.3969/j.issn.2095-9400.2019.12.010

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摘要目的：探讨钙蛋白酶1（CANP1）及其相关信号通路在瑞芬太尼诱发切口痛大鼠痛觉过敏中的作用。方法：以尾静脉和鞘内置管合格的SD大鼠建立切口痛模型，设立对照组、瑞芬太尼组、瑞芬太尼+U0126组和瑞芬太尼+Calpeptin组；瑞芬太尼诱发模型切口疼痛，MEK激酶抑制剂U0126预处理抑制脊髓MEK活性，钙蛋白酶（CANP）特异性抑制剂Calpeptin预处理干预脊髓CANP活性；于静脉给药前24 h、静脉给药后2、6、24和48 h（T0～T4）时测定机械缩足反应阈（MWT）和热缩足潜伏期（TWL），Western blot法检测ERK、CANP1及GSK-3β蛋白表达水平。结果：对照组大鼠T0～T4时间MWT和TWL无明显变化（P＞0.05）；与对照组比，T1～T4瑞芬太尼组大鼠MWT降低，TWL缩短（均P＜0.01）；与瑞芬太尼组比，T1～T4瑞芬太尼+U0126组和瑞芬太尼+Calpeptin组MWT和TWL均升高（P＜0.05或P＜0.01）；给药后48 h与对照组比，瑞芬太尼组p-ERK蛋白和CANP1大亚基自身水解蛋白（Cleaved-CANP1）表达明显上调（P＜0.01）；与瑞芬太尼组比，瑞芬太尼+U0126组p-ERK蛋白表达明显下调（P＜0.01）；与瑞芬太尼组比，瑞芬太尼+Calpeptin组p-ERK蛋白表达无明显变化（P＞0.05）；与瑞芬太尼组比，瑞芬太尼+U0126和瑞芬太尼+Calpeptin组Cleaved-CANP1明显减少（P＜0.01）。给药后48 h与对照组比，瑞芬太尼组大鼠GSK-3β和pGSK-3β/GSK-3β相对蛋白表达量均明显升高（P＜0.01）；而与瑞芬太尼组比，瑞芬太尼+U0126组和瑞芬太尼+Calpeptin组GSK-3β和pGSK-3β/GSK-3β相对蛋白表达量明显减少（P＜0.01）。结论：瑞芬太尼诱导的疼痛过敏作用可能与激活ERK/CANP1/GSK-3β信号通路有关。

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	黄燕
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关键词 ：瑞芬太尼, 钙蛋白酶1, 脊髓, 痛觉过敏, 机制

Abstract：Objective: To investigate the role of calpain 1 (CANP1) and its related signaling pathway in hyperalgesia induced by remifentanil in rats with incisional pain. Methods: Incisional pain model was established in SD rats qualified for tail vein and sheath tube. The control group, remifentanil group, remifentanil+U0126 group and remifentanil+Calpeptin group were established. Remifentanil induced model incision pain. Pretreatment with MEK kinase inhibitor U0126 inhibited MEK activity in the spinal cord. Calmodulin (CANP)-specific inhibitor Calpeptin pretreatment intervened with CANP activity in the spinal cord. Mechanical contraction threshold (MWT) and heat-shrinking latency (TWL) were measured 24 h before intravenous infusion of saline or remifentanil, 2, 6, 24, and 48 h after intravenous administration (T0-T4). The mechanical contraction threshold (MWT) and heat-shrinking latency (TWL) were measured at 24 h before intravenous administration and 2, 6, 24, 48 h after intravenous administration (T0-T4). The protein expression levels of ERK, Calpain1 and GSK-3β were detected by Western blot. Results: There was no significant change in MWT and TWL in the control group at T0-T4. The MWT of the rats in the remifentanil group gradually decreased, and the TWL gradually shortened. The difference in the time points between the two groups was statistically significant (P<0.01). Compared with the remifentanil group, both the remifentanil+U0126 group and the remifentanil+calpeptin group had higher MWT and TWL at each time point (P<0.05 or P<0.01). Compared with the control group, the expression of p-ERK protein and CANP1 large subunit hydrolyzed protein (Cleaved-CANP1) was significantly up-regulated in the remifentanil group (P<0.01). Compared with the remifentanil group, the expression of p-ERK protein was significantly down-regulated in the remifentanil+U0126 group (P<0.01), and there was no significant change in the remifentanil+Calpeptin group. Compared with the control group, the relative protein expressions of GSK-3β and pGSK-3β/GSK-3β in the remifentanil group were significantly increased (P<0.01). Compared with the remifentanil group, the relative protein expression levels of GSK-3β and pGSK-3β/GSK-3β were significantly decreased in the remifentanil+U0126 group and remifentanil+Calpeptin group (P<0.01). Conclusion: The pain allergic effect induced by remifentanil may be related to the activation of ERK/CANP1/GSK-3β signaling pathway.

Key words： remifentanil calpain 1 spinal cord hyperalgesia mechanism

收稿日期: 2019-05-16

作者简介: 黄燕（1989-），女，浙江丽水人，住院医师。

链接本文:

https://xb.wmu.edu.cn/CN/10.3969/j.issn.2095-9400.2019.12.010 或 https://xb.wmu.edu.cn/CN/Y2019/V49/I12/905

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