抑制Nod样受体蛋白3减轻大鼠蛛网膜下腔出血后血脑屏障破坏和神经功能缺损的研究  

Suppression of NLRP3 attenuates blood-brain barrier disruption and neurological deficits in rats following subarachnoid hemorrhage

作　　者：俞书红 郭志良[1] 王刘敏 陈万红[1] 张仁良[1] 刘新峰[1] 

机构地区：[1]南京大学医学院附属金陵医院(南京军区南京总医院)神经内科,210002

出　　处：《中华老年心脑血管病杂志》2016年第6期641-644,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：江苏省自然科学基金(BK2011663)

摘　　要：目的观察慢病毒介导的Nod样受体蛋白3(NLRP3)特异性RNA干扰对大鼠蛛网膜下腔出血(SAH)后血脑屏障破坏及神经功能缺损的作用。方法 SD雄性大鼠44只,随机分为4组;假手术组(Sham组)8只,SAH组12只,阴性对照病毒组(LV-Control组)12只,NLRP3慢病毒干扰组(LV-shNLRP3组)12只;后3组均行血管内刺破法SAH造模。SAH后24h行Western blot、ABC/DAB染色、改良Garcia评分及平衡木实验,观察SAH造模24h后,4组大鼠NLRP3蛋白表达、血脑屏障结构成分表达、血脑屏障渗漏变化及神经功能缺损情况。结果 NLRP3在Sham组呈现低水平表达,SAH组及LV-Control组显著升高(P<0.01);LV-shNLRP3组显著减少(P<0.05)。SAH组及LV-Control组血脑屏障完整性标记物(ZO-1、occludin、VE-cadherin)表达显著下降(P<0.01);而LVshNLRP3组显著升高(P<0.05),且IgG渗出明显减少。结论慢病毒介导的RNA干扰抑制NLRP3,能减轻大鼠SAH后血脑屏障破坏和神经功能缺损。Objective To study the inhibitory effect of lentivirus（LV）-mediated NLRP3 RNAi on blood-brain barrier（BBB）disruption and neurological deficits in rats following subarachnoid hemorrhage（SAH）.Methods Forty-four male SD rats were randomly divided into sham group（n=8）,SAH group（n=12）,LV-control group（n=12）,and LV-shNLRP3group（n=12）.Twentyfour hours after a SAH model was established by endovascular perforation for the later 3groups,expressions of NLRP3 and BBB structure junction elements,BBB leakage and neurological deficits were detected by Western blot,modified Garcia test and beam-walking test respectively with ABC/DAB staining.Results The expression level of NLRP3 was significantly higher in SAH group and LV-control group than in sham operation group and was significantly lower in LV-shNLRP3 group than in sham operation group（P〈0.01）.The expression level of BBB integrity markers（ZO-1,occludin,VE-cadherin）was significantly lower in SAH group and LV-control group than in sham operation group（P〈0.01）and was significantly higher in LV-shNLRP3 group than in sham operation group（P〈0.05）.However,the BBB leakage was significantly less in LV-shNLRP3 group than in sham operation group.Conclusion Suppression of LV-mediated NLRP3 RNAi can attenuate BBB disruption and neurological deficits in rats following SAH.

关 键 词：蛛网膜下腔出血 RNA干扰 血脑屏障 慢病毒属 

分 类 号：R743.35[医药卫生—神经病学与精神病学]