摘要
目的:研究NLRP3炎性小体在大鼠蛛网膜下腔出血(SAH)早期脑损伤(EBI)过程中对血脑屏障(BBB)的影响。方法:36雄性SD大鼠分为假手术组(sham)、SAH组(SAH)和NLRP3抑制剂MCC950处理组(SAH+MCC950),利用注射自体血液的方法制备SAH大鼠模型,利用尾静脉注射给予SAH大鼠MCC950处理。利用改良神经功能缺损评测大鼠神经功能变化,利用伊文斯蓝渗透实验(EBP)检测BBB的完整性,利用Western Blot方法检测大鼠脑组织中NLRP3和claudin-1等分子的表达变化,利用酶联免疫吸附试验(ELISA)试剂盒检测脑组织中细胞因子肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)的水平。结果:SAH组大鼠神经功能严重受损,血脑屏障完整性破坏,NLRP3表达增加,claudin-1的表达下降,SAH大鼠脑组织中TNF-α和IL-1β水平显著增加。给予MCC950处理的大鼠神经功能有了显著改善,血脑屏障完整性破坏程度减轻,NLRP3表达下降,claudin-1的表达部分恢复,TNF-α和IL-1β水平显著降低。结论:NLRP3通过下调claudin-1表达增加早期SAH大鼠BBB通透性,这一机制可能参与了SAH大鼠EBI的发生。
Objective:To investigate the effect of NOD-like receptor(NLR)family,pyrin domain-containing protein 3(NLRP3)inflammasome on the blood-brain barrier(BBB)during early brain injury(EBI)in rats with subarachnoid hemorrhage(SAH).Methods:36 male SD rats were divided into sham operation group(Sham),SAH group(SAH),and NLRP3 inhibitor MCC950 treatment group(SAH+MCC950).The SAH rat model was prepared by injecting autologous blood.The neurological function changes of the rats were evaluated by using improved neurological deficits.The integrity of the BBB was detected by Evans blue permeation(EBP).The expressions of NLRP3 and claudin-1 in rat brain tissue were detected by Western Blot.The levels of cytokines TNF-αand IL-1βin brain tissue were detected by enzyme linked immunosorbent assay(ELISA).Results:SAH surgery resulted in severe neurological impairment,impaired blood-brain barrier integrity,increased NLRP3 expression,decreased claudin-1 expression,and significantly increased TNF-αand IL-1βlevels in brain tissue of rat.However,the SAH rats treated with MCC950 showed significant improvement in neurological function,reduced impairment of BBB integrity,decreased NLRP3 expression,partially restored claudin-1 expression,and significantly reduced levels of TNF-αand IL-1β.Conclusion:NLRP3 increased BBB permeability in rats with early subarachnoid hemorrhage by down-regulating claudin-1 expression,which may be involved in EBI of SAH rats.
作者
董玉书
赵忠惠
郝广志
邹正
梁国标
Dong Yushu;Zhao Zhonghui;Hao Guangzhi;Zou Zheng;Liang Guobiao(Institute of Neuroscience,General Hospital of Northern Theater Command Base,Shenyang 110016,China)
出处
《神经解剖学杂志》
CAS
CSCD
2021年第1期67-71,共5页
Chinese Journal of Neuroanatomy
基金
国家自然科学基金(81671313,82071481)
全军医学科技青年培育计划拔尖项目(17QNP053)
中国博士后科学基金面上资助(2016M592951)。
