摘要
目的 探究Nrf-2/HO-1信号通路调节的Mfsd2a表达在缺血性脑卒中(IS)引起的血-脑脊液屏障(BCFB)破坏中的作用。方法 45只健康雄性SD大鼠,随机分为假手术组,脑缺血组,脑缺血+BARD组。取非假手术组大鼠,参考Longa法构建IS模型,取脑缺血+BARD组大鼠立即尾静脉注射2.0mg·kg^(-1) BARD。24 h后开展神经功能评估,之后分别检测大鼠脑梗死体积,BCFB通透性,脑水肿程度,最后采用免疫荧光和Western blot检测各个蛋白表达。结果 IS造成大鼠神经功能评分增加,脑组织出现梗死区域,BCFB通透性与脑水肿程度增加。与脑缺血组相比,BARD下调了大鼠神经功能评分,减少了梗死体积,降低了BCFB通透性与脑水肿程度。分子水平上,BARD治疗进一步激活了Nrf-2/HO-1信号通路,增加了Mfsd2a表达。与此同时,BARD干预逆转了IS造成的BCFB紧密连接蛋白Claudin-5、ZO-1与VEcadherin表达降低。结论 Nrf-2/HO-1信号通路激活介导Mfsd2a表达增加,促进了BCFB修复,减轻了脑水肿与脑梗死,改善了IS大鼠神经功能损伤。
Objective To explore the role of Mfsd2 a regulated by the Nrf-2/HO-1 pathway in the destruction of the blood-cerebrospinal fluid barrier(BCFB) caused by ischemic stroke(IS).Methods 45 healthy male SD rats were randomly divided into sham group,ischemia group,and ischemia+BARD group.The rats in the non-sham group were taken for IS model construction referring to the Longa method.The rats in the ischemia+BARD group were immediately injected with 2.0 mg·kg^(-1) BARD through the tail vein.After 24 hours,all rats were evaluated for neurological function,and then the cerebral infarction volume,BCFB permeability,and degree of cerebral edema were detected respectively.Finally,the expression of each protein was detected by immunofluorescence and Western blot.Results The establishment of IS model caused an increase in the neurological score,and resulted in an infarct area in brain,an increase in the permeability of the blood brain barrier and the degree of cerebral edema.Compared with ischemia group,BARD treatment down-regulated the neurological score,reduced the infarct volume,and reduced the permeability of the BCFB and the degree of cerebral edema.On the molecular level,administration of BARD further activated the Nrf-2/HO-1 signaling pathway and increased the expression of Mfsd2 a.At the same time,BARD intervention reversed the decreased expression of BCFB tight junction proteins like Claudin-5,ZO-1 and VE-cadherin caused by IS.Conclusion The activation of the Nrf-2/HO-1 signaling pathway mediates the increase of Mfsd2 a expression,promotes the repair of the BCFB,reduces cerebral edema and cerebral infarction,and improves the neurological damage in rats with ischemic stroke.
作者
胡琼文
李乐雯
吴妹
赖天宝
Hu Qiongwen;Li Lewen;Wu Mei;Lai Tianbao(Department of Geriatric Rehabilitation,the Hainan Provincial Cadre Sanatorium(Hainan Provincial Hospital for Geriatrics),Haikou 571100,China)
出处
《脑与神经疾病杂志》
CAS
2022年第6期380-384,共5页
Journal of Brain and Nervous Diseases
基金
福建省卫生计生青年科研课题(2016-2-66)。
