NLRP3通过下调claudin-1增加早期蛛网膜下腔出血大鼠血脑屏障通透性

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MCC95...

NLRP3 increased blood-brain barrier permeability in rats with early subarachnoid hemorrhage by down-regulation of claudin-1

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.