国际麻醉学与复苏杂志
國際痳醉學與複囌雜誌
국제마취학여복소잡지
INTERNATIONAL JOURNAL OF ANESTHESIOLOGY AND RESUSCITATION
2009年
3期
231-235
,共5页
史长喜%马正良%钟好%张伟%杨磊%顾小萍
史長喜%馬正良%鐘好%張偉%楊磊%顧小萍
사장희%마정량%종호%장위%양뢰%고소평
神经病理性疼痛%脊髓%JWH015%NR2B亚基%磷酸化
神經病理性疼痛%脊髓%JWH015%NR2B亞基%燐痠化
신경병이성동통%척수%JWH015%NR2B아기%린산화
Neuropathic pain%Spinal cord%JWH015%NR2B subunit%Phosphorylation
目的 研究鞘内注射CB2受体激动剂JWH015对背根节慢性压迫(chronic compression of the dorsal root ganglia,CCD)大鼠痛阈和脊髓背角磷酸化NMDA受体NR2B亚基表达的影响,探讨CB2受体激动剂的镇痛作用及其可能机制.方法 鞘内置管成功后的雄性SD大鼠84只,随机分为3组:假手术+50%二甲基亚砜(dimethyl sulphoxide,DMSO)组(Sham组)、CCD+50%DMSO组(Vehicle组)、CCD+JWH015组(JWH015组).Sham组和Vehicle组各有6只大鼠在假手术或CCD后第7天(鞘内未给药)取脊髓标本,作为免疫组织化学法检测脊髓背角Tyr-1472磷酸化NR2B亚基表达的基础值.其余大鼠在假手术或CCD后第7天分别鞘内注射50%DMS010μl或JWH015 10μg.假手术或CCD之前、鞘内给药之前、之后1、2、4、8、24、72 h分别记录机械刺激缩足反射阈值(paw withdrawal mechanical threshold,PWMT)和热刺激缩足反射潜伏期(paw withdrawalthermal latency,PWTL)(n=6),鞘内给药之后4、8、24、72 h分别取脊髓标本(n=6),应用免疫组织化学法检测脊髓背角Tyr-1472磷酸化NR2B亚基的表达情况.结果 鞘内给药前Vehicle组和JWH015组大鼠的PWMT和PWTL均较基础值明显下降(P<0.01);与Vehicle组相比,JWH015组在给药后1、2、4 h PWMT和PWTL显著升高(P<0.01),但在给药后8、24、72 h差异无统计学意义(P>0.05);Sham组大鼠脊髓背角Tyr-1472磷酸化NR2B业基均呈低水平表达,但在CCD后第7天表达水平明显增强;鞘内注射50%DMSO后在各时间点均未能减弱CCD大鼠脊髓背角Tyr-1472磷酸化NR2B亚基的表达;鞘内注射JWH015在给药后4、8 h能明显减弱CCD大鼠脊髓背角Tyr-1472磷酸化NR2B亚基的表达,但在给药后24、72 h Tyr-1472磷酸化NR2B亚基的表达再次增强.结论 CB2受体激动剂JWH015对大鼠的神经病理性疼痛有治疗作用,该作用可能与抑制脊髓背角Tyr-1472磷酸化NR2B亚基的表达有关.
目的 研究鞘內註射CB2受體激動劑JWH015對揹根節慢性壓迫(chronic compression of the dorsal root ganglia,CCD)大鼠痛閾和脊髓揹角燐痠化NMDA受體NR2B亞基錶達的影響,探討CB2受體激動劑的鎮痛作用及其可能機製.方法 鞘內置管成功後的雄性SD大鼠84隻,隨機分為3組:假手術+50%二甲基亞砜(dimethyl sulphoxide,DMSO)組(Sham組)、CCD+50%DMSO組(Vehicle組)、CCD+JWH015組(JWH015組).Sham組和Vehicle組各有6隻大鼠在假手術或CCD後第7天(鞘內未給藥)取脊髓標本,作為免疫組織化學法檢測脊髓揹角Tyr-1472燐痠化NR2B亞基錶達的基礎值.其餘大鼠在假手術或CCD後第7天分彆鞘內註射50%DMS010μl或JWH015 10μg.假手術或CCD之前、鞘內給藥之前、之後1、2、4、8、24、72 h分彆記錄機械刺激縮足反射閾值(paw withdrawal mechanical threshold,PWMT)和熱刺激縮足反射潛伏期(paw withdrawalthermal latency,PWTL)(n=6),鞘內給藥之後4、8、24、72 h分彆取脊髓標本(n=6),應用免疫組織化學法檢測脊髓揹角Tyr-1472燐痠化NR2B亞基的錶達情況.結果 鞘內給藥前Vehicle組和JWH015組大鼠的PWMT和PWTL均較基礎值明顯下降(P<0.01);與Vehicle組相比,JWH015組在給藥後1、2、4 h PWMT和PWTL顯著升高(P<0.01),但在給藥後8、24、72 h差異無統計學意義(P>0.05);Sham組大鼠脊髓揹角Tyr-1472燐痠化NR2B業基均呈低水平錶達,但在CCD後第7天錶達水平明顯增彊;鞘內註射50%DMSO後在各時間點均未能減弱CCD大鼠脊髓揹角Tyr-1472燐痠化NR2B亞基的錶達;鞘內註射JWH015在給藥後4、8 h能明顯減弱CCD大鼠脊髓揹角Tyr-1472燐痠化NR2B亞基的錶達,但在給藥後24、72 h Tyr-1472燐痠化NR2B亞基的錶達再次增彊.結論 CB2受體激動劑JWH015對大鼠的神經病理性疼痛有治療作用,該作用可能與抑製脊髓揹角Tyr-1472燐痠化NR2B亞基的錶達有關.
목적 연구초내주사CB2수체격동제JWH015대배근절만성압박(chronic compression of the dorsal root ganglia,CCD)대서통역화척수배각린산화NMDA수체NR2B아기표체적영향,탐토CB2수체격동제적진통작용급기가능궤제.방법 초내치관성공후적웅성SD대서84지,수궤분위3조:가수술+50%이갑기아풍(dimethyl sulphoxide,DMSO)조(Sham조)、CCD+50%DMSO조(Vehicle조)、CCD+JWH015조(JWH015조).Sham조화Vehicle조각유6지대서재가수술혹CCD후제7천(초내미급약)취척수표본,작위면역조직화학법검측척수배각Tyr-1472린산화NR2B아기표체적기출치.기여대서재가수술혹CCD후제7천분별초내주사50%DMS010μl혹JWH015 10μg.가수술혹CCD지전、초내급약지전、지후1、2、4、8、24、72 h분별기록궤계자격축족반사역치(paw withdrawal mechanical threshold,PWMT)화열자격축족반사잠복기(paw withdrawalthermal latency,PWTL)(n=6),초내급약지후4、8、24、72 h분별취척수표본(n=6),응용면역조직화학법검측척수배각Tyr-1472린산화NR2B아기적표체정황.결과 초내급약전Vehicle조화JWH015조대서적PWMT화PWTL균교기출치명현하강(P<0.01);여Vehicle조상비,JWH015조재급약후1、2、4 h PWMT화PWTL현저승고(P<0.01),단재급약후8、24、72 h차이무통계학의의(P>0.05);Sham조대서척수배각Tyr-1472린산화NR2B업기균정저수평표체,단재CCD후제7천표체수평명현증강;초내주사50%DMSO후재각시간점균미능감약CCD대서척수배각Tyr-1472린산화NR2B아기적표체;초내주사JWH015재급약후4、8 h능명현감약CCD대서척수배각Tyr-1472린산화NR2B아기적표체,단재급약후24、72 h Tyr-1472린산화NR2B아기적표체재차증강.결론 CB2수체격동제JWH015대대서적신경병이성동통유치료작용,해작용가능여억제척수배각Tyr-1472린산화NR2B아기적표체유관.
Objective To test whether activation of CB2 receptor would induce antinociception and investigate the role of in-trathecal JWH015 in the modulation of Tyr-1472 phosphorylation of the spinal NR2B subunit in a model of neuropathic pain. Meth-otis 84 male SD rats with intrathecal catheter insertion were randomly divided into 3 groups: sham + 50% DMSO group (Sham group); CCD + 50%DMSO group(Vehicle group); CCD+JWH015 group(JWH015 group). Seven days after Sham or CCD(without in-trathecal injection), the lumbosacral spinal cords of 6 Sham rats and 6 CCD rats were collected for immunohistochemical study to de-termine the spinal expression of Tyr-1472 phosphorylated NR2B subunit(baseline). The rest were intrathcally injected with 50%DMSO 10 μl or JWH015 10 μg seven days after Sham or CCD. For behavioral studies, the data of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in Sham group or CCD group, before intrathecal injection and 1, 2, 4, 8, 24, 72 h after intrathecal injection (n=6). For immunohistochemical study, the lumbosacral spinal cords were collected 4, 8, 24, 72 h after intrathecal injection(n=6). Results Compared with the baseline before operation, the PWMT and the PWTL of Vehicle group and JWHOI5 group began to decrease before intrathecal injection(P<0.01). Compared with Vehicle group, PWMT and PWTL of JWH015 group increased markedly 1, 2 and 4 h after intrathecal injection (P<O.01), but there was no statistical difference 8, 24 and 72 h after intrathecal injection (P>0.05). Tyr-1472 phosphorylated NR2B subunit expression in the superficial dorsal horn was weak in all sham groups, but increased significantly 7 days after CCD. While intrathecal 50%DMSO did not decrease the expres-sion of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn, the expression of Tyr-1472 phosphorylated NR2B sub-unit in the superficial dorsal horn decreased obviously 4 h and 8 h after intrathcal JWH015. However, the expression of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn increased again 24 h and 72 h after intrathcal JWH015. Conclusion In-trathecal administration of CB2 receptor agonist JWHOI5 may provide analgesic effect, which is probably attributed to the decrease in the spinal expression of Tyr-1472 phosphorylated NR2B subunit.
