鞘内注射MRS2395及MRS2211对足烫伤大鼠机械痛及炎症因子表达的影响  

The effect of intrathecal injected of MRS2395 and MRS2211 on the mechanical pain and the expression of inflammatory factors in dorsal spinal cord of hindpaw burn injury rats

作　　者：徐陶[1] 詹顺 杨俊娜[1] 何丽[1] 徐瑞 杨帆[1] 许阿香 曾俊伟[1] Xu Tao;Zhan Shun;Yang Junna;He Li;Xu Rui;Yang Fan;Xu Axiang;Zeng Junwei(Department of Physiology,Zunyi Medical College,Guizhou Key Laboratory of Anesthesia and Organ Protection,Zunyi 563000,China)

机构地区：[1]遵义医学院生理学教研室贵州省麻醉与器官功能保护重点实验室,遵义563000

出　　处：《神经解剖学杂志》2018年第4期447-453,共7页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(1460266;31640040);教育部新世纪优秀人才计划(NCET-13-1070);贵州省遵义市科学技术联合基金(遵市科合社字2016-26号)

摘　　要：目的:观察鞘内注射P2Y_(12)受体拮抗剂MRS2395和/或P2Y_(13)受体拮抗剂MRS2211对足烫伤大鼠机械痛以及脊髓背角炎症因子IL-1β、IL-6和TNF-α表达的影响。方法:在烫伤前1 h、烫伤后第6、12、24和48 h测定给药后机械缩足反应阈值(MWT);烫伤后24 h,取脊髓背角,实时荧光定量PCR检测Iba-1、IL-1β、IL-6和TNF-αm RNA表达,ELISA技术检测背角IL-1β、IL-6和TNF-α含量。结果:与假烫伤组相比,大鼠烫伤后6 h即出现MWT明显下降,持续24 h处于较低水平(P<0.01),但48 h后MWT回升。与烫伤组相比,单独鞘内注射MRS2395或MRS2211组12 h后MWT升高(P<0.05),联合给药组MWT升高更为明显(P<0.01)。与假烫伤组相比,烫伤大鼠脊髓背角Iba-1、IL-1β、IL-6和TNF-αm RNA表达明显上调(P<0.01),IL-1β、IL-6和TNF-α水平上调(P<0.01)。单独鞘内注射MRS2395或MRS2211仅部分抑制烫伤大鼠脊髓背角Iba-1、IL-1β、IL-6和TNF-αm RNA表达上调(P<0.05)以及部分抑制烫伤大鼠脊髓背角IL-1β、IL-6和TNF-α水平上升(P<0.05)。MRS2395和MRS2211联合鞘内注射几乎完全阻断烫伤大鼠脊髓背角Iba-1、IL-6和TNF-αm RNA表达上调(P<0.01),仅部分阻断IL-1β表达上调(P<0.05),以及几乎完全阻断烫伤引起的脊髓背角IL-6和TNF-α水平上升(P<0.01),仅部分阻断IL-1β水平上升(P<0.05)。结论:单独鞘内注射MRS2395或MRS2211能够缓解烫伤痛大鼠机械痛敏症状,但联合用药时,镇痛效果更佳,其机制可能与抑制脊髓背角小胶质细胞激活以及炎症因子IL-1β、IL-6和TNF-α表达上调有关。Objective：The aim of this study is to investigate the effect of intrathecal injected antagonist MRS2395 and/or MRS2211 of P2Y（12） and P2Y（13） receptor on the mechanical pain and the expression of inflammatory factors IL-1β,IL-6 and TNF-α in dorsal spinal cord of rat with foot burn injury.Methods：The mechanical withdrawal threshold（MWT） was evaluated before burning and on 6,12,24 and 48 h after burning.The expression of Iba-1,IL-1β、IL-6 and TNF-α in dorsal spinal cord was examined by real time RT-PCR on 24 h after burn injury.At the same time,the contentof IL-1β,IL-6 and TNF-α in dorsal spinal cord was examined by ELISA.Results：After burn injury,MWT was significantly decreased at 6,12 and 24 h than sham group（P〈0.05）.However,compare with sham group,burn-injured rats at 48 h do not displayed obvious mechanical allodynia.Repeated intrathecal administration of MRS2395 or MRS2211 significantly suppressed this decrease in MWT at 6,12 and 24 h after burning（MRS2395：P〈0.05;MRS2211：P〈0.05）.Co-administration of MRS2395 and MRS2211 obvious ameliorated bury injury-induced mechanical hypersensitivity（P〈0.01）.Compared with sham group,the expression of Iba-1,IL-1β,IL-6 and TNF-α m RNA was significantly increased in dorsal spinal cord at 24 h after burn injury（P〈0.01）.the content of IL-1β,IL-6 and TNF-α were significantly increased in dorsal spinal cord of burn-injured rats（24 h：P〈0.01）.Compared with burn group,repeated intrathecal administration of MRS2395 or MRS2211 partially inhibited the increased expression of Iba-1,IL-1β,IL-6 and TNF-α m RNA（MRS2395：P〈0.05;MRS2211：P〈0.05）.And partially inhibited the increased content of IL-1β,IL-6 and TNF-α at 24 h after burn injury（MRS2395：P〈0.05;MRS2211：P〈0.05）.Co-administration of MRS2395 and MRS2211 almost completely blocked the increased expression of Iba-1,IL-6 and TNF-α m RNA after bury injury（P〈0.01）.However,the expression of IL-1β m RNA was only partially inhibited after MRS2395

关 键 词：烫伤痛 脊髓背角 P2Y12受体 P2Y13受体 大鼠 

分 类 号：R644[医药卫生—外科学]