前列腺素EP4受体激动剂HY-128686对实验性缺血性脑梗死的神经保护作用  

Neuroprotective effect of prostaglandin EP4 receptor agonist HY-128686 on experimental cerebral ischemic stroke

作　　者：罗彩琴[1] 荆忻[1] 沈佳[1] 马晓薇[1] 朱金源[1] Luo Caiqin;Jing Xin;Shen Jia;Ma Xiaowei;Zhu Jinyuan(Intensive Care Unit,General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学总医院重症监护室,银川750004

出　　处：《解剖学杂志》2021年第4期300-306,共7页Chinese Journal of Anatomy

基　　金：宁夏自然科学基金(2020AAC03378)。

摘　　要：目的:研究前列腺素EP4受体激动剂HY-128686对大鼠短暂性局灶性脑缺血的治疗作用及其机制。方法:采用线栓法制备大鼠大脑中动脉闭塞模型,使用不同剂量HY-128686或空白溶剂处理后,大鼠进行神经系统缺陷评估,收集脑样本,计算梗死面积,检测基质金属蛋白酶9(MMP-9)、白介素6(IL-6)、白介素1β(IL-1β)以及血管紧密结合蛋白的表达变化。结果:HY-128686处理可以显著减少大鼠脑梗死体积,降低MMP-9,抑制IL-1β、IL-6以及紧密结合蛋白-1的表达,促进神经功能恢复。结论:HY-128686通过激活EP4减少炎症前因子IL-1β和IL-6以及MMP-9表达,从而抑制紧密连接蛋白的降解,减少脑梗死面积发挥神经保护作用。Objective:To study the protective effect and mechanism of prostaglandin EP4 receptor agonist HY-128686 on transient focal cerebral ischemia in rats.Methods:The rat middle cerebral artery occlusion model was prepared by the suture method.After treatment with different doses of HY-128686 or blank solvent,the rats were evaluated for neurological deficits,samples were collected,infarct size was calculated,and changes in the expression of matrix metalloprotein 9(MMP-9),interleukin 6(IL-6),interleukin 1β(IL-1β)and vascular tight binding protein were detected.Results:HY-128686 treatment significantly reduced the rat cerebral infarction volume,reduced MMP-9,inhibited the expression of IL-1β,IL-6 and zonula occludens-1,and promoted the recovery of nerve function.Conclusion:HY-128686 reduces the expression of pre-inflammatory factors including IL-1β,IL-6 and MMP-9 by activating EP4.As a result,the degradation of tight junction protein is inhibited,the integrity of blood brain barrier is maintained,and the infarct area to exert neuroprotective effects is reduced.

关 键 词：缺血性脑梗死 血脑屏障 前列腺素EP4受体 炎症因子 基质金属蛋白酶 

分 类 号：R743.33[医药卫生—神经病学与精神病学]