糖皮质激素对焦虑大鼠机械性痛觉过敏的影响

The effect of glucocorticoids on anxiety-induced mechanical hyperalgesia in rats

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1h腹腔注射25 mg/kg美替拉酮.在SPS造模后1d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）.②Western 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.

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-maze test,the number of entries and the percentage of time spent in open-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.