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#

doi:10.16098/j.issn.0529-1356.2020.02.003

解剖学报 ›› 2020, Vol. 51 ›› Issue (2): 167-171.doi: 10.16098/j.issn.0529-1356.2020.02.003

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#

彭志锋^1*刘颖¹ 牛春红²

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

收稿日期:2019-03-14 修回日期:2019-04-06 出版日期:2020-04-06 发布日期:2020-04-06
通讯作者: 彭志锋 E-mail:pzf181@126.com
基金资助:
山西省基础研究项目

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

PENG Zhi-feng^1* LIU Ying¹ NIU Chun-hong²

1. Department of Physiology, Medical College of Shanxi Datong University, Shanxi Datong 037009,China; 2. Department of Pathophysiology, Medical College of Shanxi Datong University, Shanxi Datong 037009,China

Received:2019-03-14 Revised:2019-04-06 Online:2020-04-06 Published:2020-04-06
Contact: PENG Zhi-feng E-mail:pzf181@126.com

摘要/Abstract

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。

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

Abstract:

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.

Key words: Ischemia/reperfusion injury, Transient receptor potential vanilloid-1, AMG517, Neurobehavioral score, Real-time PCR, Enzyme inked immunosorbent assay, Mouse

中图分类号:

R743.31

彭志锋刘颖牛春红. 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#[J]. 解剖学报, 2020, 51(2): 167-171.

PENG Zhi-feng LIU Ying NIU Chun-hong. 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[J]. Acta Anatomica Sinica, 2020, 51(2): 167-171.

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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#

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

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