晚期糖化终产物受体中和抗体缓解腰5脊神经结扎大鼠神经病理性疼痛的效果观察  

Alleviation of allodynia in the rat model of spinal nerve ligation by intrathecal receptor for advanced glycation end product neutralizing antibody

作　　者：李向南[1] 李永华[1] 袁红斌[1] 

机构地区：[1]第二军医大学附属长征医院麻醉科,上海200003

出　　处：《海军医学杂志》2015年第3期205-208,212,共5页Journal of Navy Medicine

基　　金：国家自然科学基金项目(81871054);上海市教育委员会科研创新项目(14ZZ083)

摘　　要：目的观察大鼠腰5脊神经结扎后注射晚期糖化终产物受体（RAGE）中和抗体的镇痛效果,探讨其在背根神经节发挥作用的机制。方法雄性SD大鼠,体质量200~250 g,采用结扎腰5脊神经（L5）制备神经根结扎（SNL）模型。30只雄性SD大鼠按数字表法随机分为3组,每组10只。分别为药物组（SNL术后每天鞘内注射RAGE中和抗体）、对照组（假手术后＋磷酸缓冲盐溶液）、安慰剂组（SNL术＋磷酸缓冲盐溶液）。于术前及术后不同时点测定大鼠的机械撤爪阈值和热刺激缩爪潜伏期。取大鼠背根神经节,进行免疫荧光染色,采用ELISA检测各组中肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β的表达。结果 SNL术后,L5背根神经节RAGE平均荧光强度（42.80±4.19）比术前（19.78±4.19）增高,差异有统计学意义（P〈0.05）。安慰剂组大鼠术后1、3、5、7 d机械缩爪阈值（9.30±2.10,4.60±1.35,3.80±1.40,3.60±1.26）与对照组（13.00±2.58,12.50±2.64,13.50±2.42,13.00±2.58）比较差异有统计学意义（P〈0.05）。安慰剂组大鼠术后1、3、5、7 d热刺激缩爪潜伏期（10.01±1.16,5.40±1.51,4.32±1.16,4.40±1.43）与对照组（12.80±1.14,13.00±1.25,12.70±1.34,12.80±1.55）比较差异有统计学意义（P〈0.05）。药物组大鼠术后3、5、7 d机械缩爪阈值（8.00±2.31,7.40±2.12,7.20±1.93）与安慰剂组（4.60±13.50,3.50±1.14,3.60±1.26）比较差异有统计学意义（P〈0.05）。药物组大鼠术后3、5、7 d热刺激缩爪潜伏期（8.15±1.37,8.26±1.29,7.00±1.07）与安慰剂组（5.41±1.51,4.32±1.16,4.40±1.43）比较差异有统计学意义（P〈0.05）。药物组大鼠术后L5背根神经节TNF-α表达量（70.53±6.57）与安慰剂组（109.90±4.97）比较差异有统计学意义（P〈0.05）。药物组大鼠术后L5背根神经节IL-1β表达量（88.24±3.60）与安慰剂组（168.77±6.34）比较差异有统计学意义（P〈0.05）。结论 RAGE中和抗Objective To observe the effect of receptor for advanced glycation end products（ RAGE） neutralizing antibody injection on neuropathic pain and the expression of TNF-α and interleukin-1β in the dorsal root ganglion（ DRG）. Methods The SNL model was developed by using adult male Sprague-Dawley rats with a body mass of 200- 250 g. Thirty animals were randomly divided into 3 groups： the drug group,the control group and the placebo group,each consisting of 10 animals. The drug group was injected with anti-RAGE intrathecally,after development of the SNL model. The control group was infused with phosphate buffered saline（ PBS） after sham surgery. And the placebo group was infused with PBS after SNL surgery. Paw withdrawal thresholds（ PWT） and paw thermal withdraw latency（ PTWL） of each group were detected at different time points both before and after surgery. The dorsal root ganglions were collected for immunohistochemistry and determination of the expression levels of TNF-α and interleukin-1β in the 3groups. Results The expression level of RAGE in L5 DRG was increased after SNL surgery,as compared with that before surgery（ 42. 80 ± 4. 19 versus 19. 78 ± 4. 19）（ P 0. 05）. When compared with those of the control group,there were significant reductions in PWT（ 9. 30 ± 2. 10 versus 13. 00 ± 2. 58,4. 60 ± 1. 35 versus 12. 50 ± 2. 64,3. 80 ± 1. 40 versus 13. 50 ± 2. 42,3. 60 ± 1. 26 versus13. 00 ± 2. 58） and in PTWL（ 10. 01 ± 1. 16 versus 12. 80 ± 1. 14,5. 40 ＋ 1. 51 versus 13. 00 ± 1. 25,4. 32 ± 1. 16 versus 12. 7 ± 1.34,4. 40 ± 1. 43 versus 12. 80 ± 1. 55） for the placebo group at days 1,3,5 and 7（ P 0. 05）. When compared with those of the placebo group,significant elevations could be seen in PWT（ 8. 00 ± 2. 31 versus 4. 60 ± 13. 50,7. 40 ± 2. 12 versus 3. 50 ± 1. 14,7. 20 ± 1. 93 versus 3.60 ± 1. 26） and in PTWL（ 8. 15 ± 1. 37 versus 5. 41 ± 1. 51,8. 26 ± 1. 29 versus 4. 32 ± 1. 16,7. 00 ± 1. 07 versus 4. 40 ± 1. 43） at days 3,5 and7 for

关 键 词：神经病理性疼痛 晚期糖化终产物受体 肿瘤坏死因子α 白细胞介素1Β 

分 类 号：R651[医药卫生—外科学]