摘要
目的:通过观察坐骨神经压迫模型CCI(chronic constriction injury,CCI)和脊神经结扎SNL(spinal nerve ligation,SNL)两种经典的神经病理性疼痛模型中自噬特异性蛋白表达,探讨两种神经病理性疼痛中自噬的改变。方法:雄性SD大鼠(200~250 g)分为CCI假手术组(sC组),CCI组(C组),CCI+腹腔注射生理盐水组(C+V组),CCI+腹腔注射氯喹组(C+C组),SNL假手术组(sS组),SNL组(S组),SNL+腹腔注射生理盐水组(S+V组),SNL+腹腔注射氯喹组(S+C组)。各组术前以及术后1、3、5、7天进行疼痛行为学测试。在术后7天sC组、C组取脊髓L4~6,sS组、S组取脊髓L4~5进行LC3、p62蛋白质免疫印迹检测。C+C组、C+V组、S+C组、S+V组检测LC3表达水平。结果:CCI模型和SNL模型产生明显的神经病理性疼痛行为学改变,注射氯喹导致机械痛阈降低;CCI模型中LC3-II、p62与假手术组相比升高;SNL模型与相应假手术组相比LC3-II升高,p62升高。C+C组和对照组相比LC3升高,S+C组与相应的对照组相比LC3升高。结论:不同神经病理性疼痛模型中自噬发生的改变不尽相同,并且抑制自噬可以增加神经病理性疼痛。增强自噬可以成为神经病理性疼痛治疗方法。
Objective： To investigate the role of autophagy in neuropathic pain. Autophagy-related proteins LC3 and p62 were analyzed in CCI and SNL models. Methods： SD rats （200-300 g） were randomly divided into eight groups （n=5）： sham CCI group （sC）, CCI group （C）, CCI＋Chloroquine group （C ＋ C）, CCI＋vehicle group （C＋V）, SNL group （S）, sham SNL group （sS）, SNL＋Chloroquine group （S＋C）, SNL＋ vehicle group （S＋V）. As a neuropathic pain-related behavioral test, mechanical withdrawal threshold （MWT） were recorded before operation （baseline） and day 1, day 3, day 5, and day 7 post operation. The expression of LC3 and p62 were examined in group sC, group C, group sS, and group S. In groups C＋C, C＋V, S＋C and S＋V, the level of LC3 was tested. Results： CCI and SNL models induced a severe reduction of neuropathic pain-related MWT, and chloroquine administration enhanced neuropathic pain. Compared with group sC, LC3 and p62 protein levels were significantly changed in group C. Compared with group sS, the expression level of LC3 and p62 were significantly increased in group S. Besides, the expression level of LC3 was significantly higher in group C＋C than that of group C＋V. In group S＋C, the LC3 level was also significantly increased compared with group S＋V. Conclusion： Autophagy in the spinal cord was differently altered in SNL and CCI models. Chloroquine, an autophagy inhibitor, administration could enhance neuropathic pain. Increasing autophagy might be a potential treatment for neuropathic pain.
出处
《中国疼痛医学杂志》
CAS
CSCD
2017年第7期489-493,共5页
Chinese Journal of Pain Medicine
基金
国家自然科学基金资助课题(No.81600971)
