N-乙酰天冬氨酰谷氨酸肽酶抑制剂对神经病理性疼痛大鼠脊髓水平瞬时感受器电位香草酸受体1表达的影响  

EFFECTS OF NAAG PEPTIDASE INHIBITOR ON THE EXPRESSION OF SPINAL TRPV1 RECEPTOR IN RATS WITH NEUROPATHIC PAIN

作　　者：李莉[1] 张苏明[1] 王存金[1] 庞君[1] 曹俊平[1] 张励才[1] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室,江苏省麻醉与镇痛应用技术重点实验室,徐州221002

出　　处：《中国疼痛医学杂志》2014年第5期295-298,共4页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金(No 30900417、30901402);江苏省高校自然科学基金(08KJB180011、9KJD320008)

摘　　要：目的：研究鞘内注射N-乙酰天冬氨酰谷氨酸（N-acetylaspartylglutamate,NAAG）肽酶抑制剂（2-PMPA）对神经病理性疼痛大鼠的镇痛作用及脊髓水平瞬时感受器电位香草酸受体1（TRPV1）表达的影响.方法：取鞘内置管成功的雄性SD大鼠24只,体重200～250 g,随机分为3组（n=8）：假手术组（sham组）、坐骨神经慢性压迫性损伤组（CCI组）和2-PMPA治疗组（2-PMPA组）.sham组只暴露坐骨神经,但不结扎,术后鞘内注射生理盐水;CCI组坐骨神经结扎后鞘内注射生理盐水;2-PMPA组坐骨神经结扎后鞘内注射2-PMPA 100 μg.所有组每次给药剂量均为10μl,每日1次,连续7d.分别于术前及术后7d时,以热缩足潜伏期（TWL）和机械缩足阈值（MWT）测定大鼠痛阈,然后处死大鼠,采用免疫荧光和Western blot法测定脊髓水平TRPV1的表达.结果：三组大鼠术后7dTWL和MWr值分别为（17.8±1.1）、（5.5±1.0）、（12.0±1.4）s和（13.1±1.2）、（4.3±0.9）、（10.5±1.0）g.与sham组比较,CCI组术后7d时TWL和MWT值均降低,脊髓TRPV1表达水平显著升高,差异有统计学意义（P＜0.05）;与CCI组比较,2-PMPA组术后7d时TWL和MWT值均升高,脊髓TRPV1表达水平显著降低,差异有统计学意义（P＜0.05）.结论：鞘内注射NAAG肽酶抑制剂可以有效地治疗神经病理性疼痛,其作用机制可能与抑制脊髓水平TRPV1的表达有关.Objective： To explore the effects of inWathecal NAAG peptidase inhibitor （2-PMPA） on pain threshold and the expression of spinal TRPV1 receptor in rots with chronic constriction injury （CCI） -induced neuropathic pain. Methods： Male SD rots weighing 200 - 250 g were used in this study. Twenty four rats in which intmthecal catheters were successfully implanted were randomly divided into 3 groups （n= 8）： sham, CCI and 2-PMPA respectively. Sciatic nerve was ligated in CCI and 2-PMPA group. Intrathecal 2-PMPA was administered every day for 7 days after sciatic nerve ligation in group 2-PMPA. In sham and CCI group, normal saline was given instead. Thermal withdraw latency （TWL） and mechanical withdrawal threshold （MWT） were measured before operation and at 7d after sciatic nerve ligation in each group, the rats were then sacrificed. Lumbar spinal cord was removed for immunofluorescent and western blotting studies to determine the expression level of TRPV1 receptor. Results： The scores of TWL （17.8± 1.1）, （5.5± 1.0）, （12.0± 1.4） and MWT （13.1±1.2）, （4.3±0.9）, （10.5± 1.0） g respectively for each group were observed after operation. Compared with sham group, TWL and MWT were decreased and the expression of TRPV1 was increased in CCI group on day 7 after sciatic nerve ligation （P 〈 0.05）; Compared with CCI group, TWL and MWT were increased and the expression of TRPV1 was decreased in 2-PMPA group onday 7 after operation （P 〈 0.05）. Conclusion： The analgesic effects of intrathecal NAAG peptidase inhibitor on neuropathic pain are possibly related to the decrease of TRPV1 receptor in the spinal cord.

关 键 词：NAAG肽酶抑制剂 神经病理性疼痛 瞬时感受器电位香草酸受体1 

分 类 号：R363[医药卫生—病理学]