自由基清除剂苯-N-叔丁基硝酮抑制大鼠脊髓损伤后中枢性痛觉敏化的行为学观察

关键词：自由基清除剂  苯-N-叔丁基硝酮  脊髓损伤  中枢性痛觉敏化  大鼠  行为学

Keywords:free radical scavenger  phenyl-N-tert-butylnitrone  spinal cord injury  hyperalgesia of central sensitization  behavior  rat

摘要：

      摘要 目的：观察不同时程自由基清除剂左旋捕集剂苯-N-叔丁基硝酮（PBN）消除活性氧（ROS）后，大鼠脊髓损伤（SCI）引发中枢性痛觉敏化的行为表现。 方法：选择健康成年雌性SD大鼠24只，体重180—220g，随机分为阴性对照组、假手术组、SCI+PBN组和SCI+生理盐水（NS）对照组（N=6）；鞘内置管后，采用自行改制的ò型纽约大学装置建立大鼠SCI模型，SCI+PBN组鞘内注射15μl PBN（3mg/15μl），SCI+NS对照组注射15μl NS，术后30min第1次注射，以后连续注射7d，每天1次；观察和记录第1、3、7、14、21、28、35天时间点大鼠对机械性和热痛敏刺激的感受性变化，并采用BBB运动功能评分标准，对术后第1、5、10、15、20、25、30、35天时间点进行行为评价。 结果：与SCI+NS对照组比较，注射SCI+PBN组大鼠机械性刺激痛阈值增高，热缩足潜伏期延长，BBB行为评价PBN注射组也明显优于对照组（P＜0.01）。 结论：左旋捕集剂苯-N-叔丁基硝酮具有消除ROS，降低中枢性痛觉敏化的作用，为进一步探讨SCI后ROS下游谷氨酸受体激活和相关细胞因子所致中枢性痛觉敏化的机制提供依据。

Abstract:

      Abstract Objective: To evaluate the behaviors of hyperalgesia after removal of reactive oxygen species（ROS） by free radical scavengers phenyl-N-tert-butylnitrone (PBN) from intrathecal injection in a rat model of central neuropathic pain after spinal cord injury (SCI). Method: Twenty-four female Sprague-Dawley rats were randomly assigned to four groups for varied purposes: control-normal, sham-operation, SCI+NS (intrathecal injection of normal saline) and SCI+PBN (intrathecal injection 15mg/15μl). A 10g rod was dropped over a distance of 25mm onto the exposed T10 cord of rats using the modified weight drop device from New York University (NYU) (150 kDyne, 1s dwell time). PBN were intrathecally injected into the damaged areas at 30min post-surgery, and continuously for 7 days. On the 1st, 5th, 10th, 15th, 20th, 25th, 30th, 35th day after SCI, BBB rating scale was used to observe the recovery of motor function. Mechanical paw withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured repeatedly before and on experimental days 1, 3, 7, 14, 21, 28, and 35 for experiment after each treatment of PBN. Result: Compared with SCI+NS and SCI+PBN groups, there were statistically significant improvements of locomotor behavior in SCI+PBN group(P＜0.05). Mechanical allodynia could be statistically significantly attenuate in SCI+PBN group compared to SCI+NS group at the same time thermal hyperalgesia could be significantly attenuate(P＜0.01). Conclusion: PBN could remove the reactive oxygen species and induce hyperalgesia of central sensitization on the SCI in rat.