芦丁通过抑制TXNIP/NLRP3信号通路减轻液压冲击脑损伤大鼠神经炎症  

Rutin alleviates neuroinflammation in rats with hydraulic shock brain injury by inhibiting the TXNIP/NLRP3 signaling pathway

作　　者：徐伟 张山[1] 杨德真 唐会昌 冯孝君 李海昌 胡程舟 XU Wei;ZHANG Shan;YANG Dezhen;TANG Huichang;FENG Xiaojun;LI Haichang;HU Chengzhou(Department of Neurosurgery,Handan Central Hospital,Handan 056000,China)

机构地区：[1]邯郸市中心医院神经外四科,056000

出　　处：《免疫学杂志》2024年第10期767-772,共6页Immunological Journal

基　　金：河北省卫生健康委医学科学研究课题计划项目(20220516)。

摘　　要：目的探索芦丁调节硫氧还蛋白互作蛋白(TXNIP)/NOD样受体蛋白3(NLRP3)信号通路对液压冲击脑损伤大鼠神经炎症的影响。方法将大鼠随机分为造模组和假手术组;造模组大鼠采用液压冲击法建立脑损伤大鼠模型,建模后随机分为芦丁低(芦丁-L,25 mg·kg^(-1)芦丁)、中(芦丁-M,50 mg·kg^(-1)芦丁)、高(芦丁-H,100 mg·kg^(-1)芦丁)剂量组、模型组以及阳性对照组(地塞米松组,0.1 mg·kg^(-1)地塞米松),每组18只。各组每天分别经药物、生理盐水干预1次,连续干预3 d后,对大鼠神经功能缺损(neurological severity score,NSS)进行评分;断头处死大鼠,测定脑水肿情况,分离挫伤灶周围脑组织,检测组织学变化,肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)炎症因子水平以及TXNIP、NLRP3蛋白表达水平。结果假手术组大鼠无损伤状况。模型组大鼠脑组织完整性被破坏,细胞皱缩核深染,间质水肿伴有空穴,TNF-α、IL-1β水平、NSS评分、脑水肿、TXNIP、NLRP3蛋白表达水平较假手术组均增加(P<0.05);经芦丁干预后,大鼠脑组织病理损伤得到缓解,TNF-α、IL-1β水平、NSS评分、脑水肿、TXNIP、NLRP3蛋白表达水平较模型组均降低(P<0.05),且芦丁-H组各项指标与地塞米松组无显著差异(P>0.05)。结论芦丁可减轻液压冲击脑损伤大鼠炎症反应,改善脑组织损伤和水肿,并抑制TXNIP/NLRP3信号通路。Objective To investigate the influence of rutin on neuroinflammation in rats with hydraulic shock brain injury by regulating thioredoxin-interacting protein(TXNIP)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods Rats were randomly separated into model group and sham operation group;the rats in the model group were established by hydraulic impact method.After modeling,they were randomly separated into rutin low(rutin-L,25 mg·kg^(-1) rutin)and medium(rutin-M,50 mg·kg^(-1) rutin).D),high(rutin-H,100 mg·kg^(-1) rutin)dose groups,model group and positive control group(dexamethasone group,0.1 mg·kg^(-1) dexamethasone),18 animals/group.Each group was intervened with drugs and normal saline once a day,and after continuous intervention for 3 days,the neurological deficit(neurological severity score,NSS)of the rats was scored;the rats were sacrificed by decapitation,the cerebral edema was determined,the brain tissue around the contusion was separated,and the histological changes,inflammatory cytokine indicators-tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)levels and TXNIP,NLRP3 protein expression levels were measured.Results The rats in the sham operation group had no injury.The integrity of brain tissue in model group was damaged,cell wrinkly nuclei were deeply stained,interstitial edema was accompanied by holes and the TNF-α and IL-1β levels,NSS score,cerebral edema,TXNIP and NLRP3 protein expression levels were all increased compared with those in the sham operation group(P<0.05);after rutin intervention,the pathological injury of rat brain tissue was relieved,and the TNF-α and IL-1β levels,NSS score,cerebral edema,TXNIP,and NLRP3 protein expression levels were all lower than those in the model group(P<0.05),there was no significant difference between the rutin-H group and the dexamethasone group(P>0.05).Conclusion Rutin can inhibit the inflammatory response of hydraulic shock brain injury rats,improve brain tissue injury and edema,which may be related to the inhibition of TXNIP/NLRP3 sign

关 键 词：芦丁 液压冲击 脑损伤 炎症 硫氧还蛋白相互作用蛋白/NOD样受体蛋白3信号通路 

分 类 号：R651.15[医药卫生—外科学]