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#br#

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。

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

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 factor α(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.