吡西达替尼抑制NLRP3通路保护脑缺血后神经功能的恢复  

The Pexidartinib inhibits NLRP3 pathway and protects neural function after cerebral ischemia

作　　者：杜小雪 邹阳 方马荣[3] Du Xiaoxue

机构地区：[1]杭州市第一人民医院,310006 [2]浙江中医药大学附属第二医院,310005 [3]浙江大学医学院,310000

出　　处：《浙江临床医学》2020年第10期1398-1400,共3页Zhejiang Clinical Medical Journal

基　　金：国家自然科学基金面上项目(81671138)。

摘　　要：目的探讨吡西达替尼抑制NLRP3信号通路改善局灶性脑缺血损伤的机制。方法参照脑缺血再灌注模型建立小鼠局灶性脑缺血模型,取50只C57/B6J小鼠,随机分为5组:正常组、假手术组(小鼠采取相同的术式,但未造模)、脑缺血组(采取常规术式)、DMSO溶剂组(腹腔注射与吡西达替尼组等体积的DMSO溶液)和吡西达替尼组[术后连续腹腔注射1mg/(kg·d)7d]。术后7d分别测定各组小鼠脑神经行为功能评分、小胶质细胞相关炎症因子及NLRP3、Caspasel,NF-κB的表达情况。结果吡西达替尼组相较于对照组,神经功能障碍程度较轻(P<0.001)。小胶质细胞相关炎症因子TNF-α、IL-10、Argl和iNOS的mRNA表达下降(P<0.01)。NLRP3蛋白、活化的Caspase1和NF-κkKB的蛋白表达降低。结论在小鼠脑缺血再灌注模型中,吡西达替尼能够降低炎症因子的表达并抑制NLRP3信号通路,缓解神经功能性障碍起到保护作用。Objective To investigate the neuroprotective mechanism of Pexidartinib in cerebral ischemia reperfusion mice model via NLRP3pathway inhibition.Methods Based on cerebral ischemia reperfusion mice model,fifty C57/B6Jmice were randomly divided into 5 groups:thecontrol group;the sham group;the cerebral ischemia reperfusion mice group;Pexidartinib treatment group with 7 days after surgery continuouslyby intraperitoneal injection(1mg/kg/day);PBS group with the equal volume of Pexidartinib.The neurobehavior dysfunction,microglia relatedinflammatory factors and NLRP3,active-Caspasel and NF-κB proteins expression were measured in each group.Results Compared with the controland sham goups,Pexidartinib treatment increased neurobehavioral score(P<0.001).Meanwhile,the mRNA expression of TNF-α,IL-10,iNOS and Argl decreased in Pexidartinib group(P<0.01)。And in the injured area,the protein expression of NLRP3,active-Caspasel and NF-κBdecreased in group when compared with control group.Conclusion Pexidartinib plays neuroprotection role in decreasing inflammation factors expressionand inhibting NLRP3 pathway to alleviating the ischemia injury.

关 键 词：脑缺血再灌注 吡西达替尼 神经炎症 NLRP3 小胶质细胞 

分 类 号：R28[医药卫生—中药学]