辣椒素受体拮抗剂AMG517在小鼠脑缺血/再灌注损伤中通过调节炎症因子释放发挥神经保护作用  

Transient receptor potential vanilloid-1 antagonist AMG517 playing a neuroprotective role in cerebral ischemia/reperfusion injury in mice by regulating the release of inflammatory factors

作　　者：彭志锋[1] 刘颖[1] 牛春红 PENG Zhi-feng;LIU Ying;NIU Chun-hong(Department of Physiology,Medical College of Shanxi Datong University,Shanxi Datong 037009,China;Department of Pathophysiology,Medical College of Shanxi Datong University,Shanxi Datong 037009,China)

机构地区：[1]山西大同大学医学院生理学教研室,山西大同037009 [2]山西大同大学医学院病理生理学教研室,山西大同037009

出　　处：《解剖学报》2020年第2期167-171,共5页Acta Anatomica Sinica

基　　金：山西省基础研究项目(2015021178);山西大同大学博士科研启动经费(2014-B-01)。

摘　　要：目的观察辣椒素受体(TRPV1)拮抗剂AMG517在小鼠脑缺血/再灌注损伤中的作用及相关机制。方法40只雄性C57BL/6小鼠随机分为假手术组(sham,n=10)、赋形剂(vehicle)+缺血/再注灌注组(vehicle,n=10)、辣椒素+缺血/再注灌注组(capsaicin,n=10)和AMG517+缺血/再注灌组(AMG517,n=10)。采用大脑中动脉闭塞(MCAO)诱导缺血/再灌注损伤,再灌注72 h进行神经行为学评分;同时检测各组小鼠梗死体积、脑水肿、TRPV1 mRNA表达和血清肿瘤坏死因子-α(TNF-α)浓度及白细胞介素-10(IL-10)浓度。结果与vehicle组相比,AMG517显著减小鼠脑梗死体积(P<0.01)。AMG517给药后也可显著降低小鼠神经行为学评分(P<0.01)。与sham组比较,vehicle组TRPV1 mRNA表达显著增加(P<0.01)。AMG517给药后可显著增加抗炎性细胞因子IL-10浓度,并降低炎性细胞因子TNF-α浓度(P<0.05)。结论AMG517可改善小鼠缺血/再灌注损伤,可能是通过缓解炎症发挥神经保护作用。Objective To investigate the effects of transient receptor potential vanilloid-1(TRPV1)antagonist AMG517 on cerebral ischemic/reperfusion injury in mice.Methods Forty male C57BL/6 mice were assigned to the following groups:sham group,vehicle+ischemia/reperfusion group(vehicle),capsaicin+ischemia/reperfusion group(capsaicin),and AMG517+ischemia/reperfusion group(AMG517).Ischemic/reperfusion injury was induced by permanent middle cerebral artery occlusion(MCAO)and neurological deficits were evaluated 72 hours after MCAO.Then,infarct volume,brain edema,mRNA expression of TRPV1 and serum concentrations of tumor necrosis factorα(TNF-α)and interleukin-10(IL-10)were measured.Results Compared with the vehicle group,AMG517 significantly decreased the infarct volume(P<0.01).Neurobehavioral score significantly decreased following administration of AMG517(P<0.01)72 hours after MCAO.Compared with the sham group,the mRNA expression of TRPV1 significantly increased in vehicle group(P<0.01).AMG517 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α(P<0.05).Conclusion AMG517 can improve ischemia/reperfusion injury in mice and may play a neuroprotective effect by alleviating inflammation.

关 键 词：缺血/再灌注损伤 辣椒素受体 AMG517 神经行为学评分 实时定量聚合酶链反应 酶联免疫吸附测定 小鼠 

分 类 号：R743.31[医药卫生—神经病学与精神病学]