首页|法舒地尔通过抑制NLRP3炎症小体激活抑制Aβ1-42诱导的小胶质细胞炎症反应

法舒地尔通过抑制NLRP3炎症小体激活抑制Aβ1-42诱导的小胶质细胞炎症反应

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目的:基于NLRP3炎症小体探讨法舒地尔减轻Aβ1-42诱导的BV2小胶质细胞损伤的机制.方法:BV2细胞分为:正常对照组、Aβ刺激组、Aβ+法舒地尔联合干预组、Aβ+MCC950(NLRP3抑制剂)联合干预组.显微镜下观察细胞形态;CCK8测定细胞活性;Griess测定NO释放量;免疫荧光染色检测NLRP3、caspase 1和IL-18表达;Western blot检测NLRP3、ASC、caspase 1、IL-1β和IL-18表达.结果:与正常对照组比较,Aβ1-42刺激组BV2细胞激活,呈阿米巴样形态,活性下降,NO释放量增加,NLRP3、ASC、caspase 1、IL-1β和IL-18表达增加.法舒地尔干预和MCC950干预均可改善Aβ1-42诱导的BV2细胞损伤,使细胞形态趋于正常,细胞活性有所增加,NO释放量降低,同时下调NLRP3、ASC、caspase 1、IL-1β和IL-18表达,两组间差异无统计学意义.结论:法舒地尔可能通过抑制NLRP3炎症小体激活减轻Aβ1-42诱导的BV2细胞损伤和炎症反应.
Fasudil inhibits Aβ1-42-induced microglial inflammatory response by inhibiting activation of NLRP3 inflammasome
Objective:To explore mechanism of Fasudil reducing Aβ1-42 induced BV2 cell injury based on NLRP3 inflamma-some.Methods:BV2 cells were divided into:normal control group,Aβ stimulation group,Aβ+Fasudil intervention group,Aβ+MCC950(NLRP3 inhibitor)intervention group.Cell morphology was observed under microscope.Cell activity was determined of by CCK8.NO release was measured by Griess.NLRP3,caspase 1 and IL-18 expressions were detected by immunofluorescence staining.NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were detected by Western blot.Results:Compared with normal control group,BV2 cells in Aβ stimulation group were activated and showed amoeba-like shape,cell activity was decreased,NO production was increased,NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were increased.Fasudil intervention and MCC950 intervention inhibited cell injury induced by Aβ1-42 in which BV2 cell morphology tended to be normal,cell activity was increased,while produc-tion of NO was reduced,and NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were down-regulated,there was no significant difference between Fasudil intervention group and MCC950 intervention group.Conclusion:Fasudil may alleviate Aβ1-42 induced BV2 cell injury and inflammatory reaction by inhibiting NLRP3 inflammasome activation.

FasudilMicrogliaNLRP3 inflammasomeInflammatory reaction

郭敏芳、章培军、于婧文、孟涛、李艳花、李娜、李梦迪、李玉璐、宋丽娟、尉杰忠、马存根

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山西大同大学脑科学研究所,大同 037009

山西中医药大学国家中医药管理局多发性硬化益气活血重点研究室/神经生物学研究中心,晋中 030619

山西医科大学生理学系,太原 030001

大同市第五人民医院,大同 037008

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法舒地尔 小胶质细胞 NLRP3炎症小体 炎症反应

山西省基础研究计划项目山西省基础研究计划项目山西省基础研究计划项目山西省卫生健康委医学科技领军团队项目国家中医药管理局多发性硬化益气活血重点研究室开放项目山西中医药大学青年科学家培育项目山西中医药大学2022年度科技创新团队项目

2021030212347620210302123475202103021233372020TD052021-KF-04T2021-PY-QN-092022TD2010

2024

中国免疫学杂志
中国免疫学会,吉林省医学期刊社

中国免疫学杂志

CSTPCD北大核心
影响因子:0.926
ISSN:1000-484X
年,卷(期):2024.40(9)