国际麻醉学与复苏杂志   2016, Issue (6): 1-1
    
糖皮质激素对焦虑大鼠机械性痛觉过敏的影响
李璐, 殷智宇, 陆翠娥, 孙绕, 马正良1()
1.南京大学医学院附属鼓楼医院
The effect of glucocorticoids on anxiety-induced mechanical hyperalgesia in rats
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摘要:

目的 探讨糖皮质激素(glucocorticoids, GCs)在焦虑诱导的机械性痛觉过敏中的作用。 方法 72只健康雄性SD大鼠分为两部分进行实验。① 行为学检测。采用完全随机分组法将24只大鼠分为3组:空白对照组(C组)、单次延长应激(single prolonged stress, SPS)模型组(A组)、SPS模型+美替拉酮组(M组),每组8只。A组和M组给予大鼠SPS进行造模,M组在SPS造模之前1 h腹腔注射25 mg/kg美替拉酮。在SPS造模后1 d进行高架十字迷宫检测3组大鼠行为学表现,同时在SPS前1 d(T0)及SPS后1 d(T1)、4 d(T2)、7 d(T3)、14 d(T4)检测大鼠机械缩足反射阈值(paw withdrawal mechanical threshold, PWMT)。② Western blot检测。共48只大鼠,A组在T0、T1、T3、T4时点用Western blot法检测大鼠脊髓糖皮质激素受体(glucocorticoid receptor, GR)的表达,每个时间点3只;在T1、T2、T3、T4时点取各组大鼠脊髓进行GR蛋白表达检测,每组3只。 结果 在高架十字迷宫实验中,A组大鼠进入开放臂次数[(4.6±1.5) 次]和开放臂停留时间比[(12.0±1.9)%]显著低于C组[(12.3±1.8) 次、(17.8±2.5)%]和M组[(9.9±1.5) 次、(16.4±3.3)%],差异有统计学意义(P<0.05)。与C组比较,A组PWMT在T1~T4时点明显下降(P<0.05);与A组比较,M组PWMT在T1~T4时点出现明显升高(P<0.05)。在SPS造模之后,大鼠脊髓GR表达明显增高(P<0.05),并增高持续到造模后14 d;与A组比较,M组GR表达水平显著降低(P<0.05)。 结论 GCs参与了焦虑诱导的机械性痛觉过敏的发展,腹腔注射美替拉酮可以缓解焦虑引起的痛觉过敏。

关键词: 糖皮质激素; 单次延长应激; 焦虑; 痛觉过敏; 美替拉酮; 大鼠
Abstract:

Objective To investigate the role of glucocorticoids(GCs) in anxiety-induced mechanical hyperalgesia in rats. Methods Seventy-two rats were divided into two part of experiments. ① Behavioral test. 24 rats were randomly divided into 3 groups(n=8): control group(C group), single prolonged stress(SPS) group(A group), SPS+metyrapone group(M group). A group and M group were exposed to SPS. Intraperitoneal injection of metyrapone(25 mg/kg) was performed 1 h before SPS procedure. Elevated plus-maze test was tested on the first day after the SPS exposure. Paw withdrawal mechanical threshold (PWMT) was test on day 1 before SPS(T0) and days 1(T1), 4(T2), 7(T3), 14(T4) after SPS. ② Western blot. 48 rats were used, glucocorticoid receptor(GR) protein expression of A group was tested by Western blot in T0, T1, T3, T4, 3 rats in each time point. GR protein expression of every group was tested by Western blot in T1, T2, T3, T4, 3 rats in each group. Results In the elevated plus?蛳maze test, the number of entries and the percentage of time spent in open?蛳arms of A group[(4.6±1.5), (12.0±1.9)%] was significantly decreased compared with C group[(12.3±1.8), (17.8±2.5)%] and M group[(9.9±1.5), (16.4±3.3)%](P<0.05). The PWMT of A group was significantly decreased on 1, 4, 7, 14 d after SPS compared with C group(P<0.05), the PWMT of M group was significantly increased on 1, 4, 7, 14 d compared with A group(P<0.05). The expression levels of glucocorticoid receptor(GR) in the spinal cord were increased significantly after SPS exposure, and it lasted 14 days(P<0.05). The expression levels of GR of M group were significantly increased compared with A group(P<0.05). Conclusions GCs are involved in anxiety-induced hyperalgesia in rats exposed to SPS. Metyrapone can significantly inhibit anxiety-induced mechanical hyperalgesia.

Key words: Glucocorticoids; Single prolonged stress; Anxiety; Hyperalgesia; Metyrapone; Rat