[1]张 言,王黎洲,杨登科,等.高密度脂蛋白抑制NLRP3对大鼠脑缺血-再灌注损伤的保护作用及其机制[J].介入放射学杂志,2019,28(08):759-764.
 ZHANG Yan,WANG Lizhou,YANG Dengke,et al.The protective effect of HDL on cerebral ischemia- reperfusion injury through inhibiting the activation of NLRP3 and its mechanism[J].journal interventional radiology,2019,28(08):759-764.
点击复制

高密度脂蛋白抑制NLRP3对大鼠脑缺血-再灌注损伤的保护作用及其机制()

PDF下载中关闭

分享到:

《介入放射学杂志》[ISSN:1008-794X/CN:31-1796/R]

卷:
28
期数:
2019年08期
页码:
759-764
栏目:
实验研究
出版日期:
2019-08-25

文章信息/Info

Title:
The protective effect of HDL on cerebral ischemia- reperfusion injury through inhibiting the activation of NLRP3 and its mechanism
作者:
张 言 王黎洲 杨登科 安天志 周 石 李 兴
Author(s):
ZHANG Yan WANG Lizhou YANG Dengke AN Tianzhi ZHOU Shi LI Xing.
School of Medical Imaging, Guizhou Medical University, Guiyang, Guizhou Province 550004, China
关键词:
【关键词】 缺血- 再灌注损伤 高密度脂蛋白 炎性小体 NOD样受体家族Pyrin 域蛋白3 脑卒中
文献标志码:
A
摘要:
【摘要】 目的 研究高密度脂蛋白(HDL)对大鼠脑缺血- 再灌注(I- R)损伤的保护作用及相关机制。 方法 构建大鼠大脑中动脉闭塞(MCAO)模型。模型组大鼠分别在缺血后1.5 h和再灌注12、24、72 h处死,取脑损伤组织用2%氯化三苯四氮唑(TTC)染色,检测再灌注损伤后不同时点脑梗死体积;根据Bederson评分标准评价大鼠神经功能;实时定量聚合酶链反应(RT- qPCR)检测脑损伤后不同灌注时间炎性小体——核苷酸结合寡聚化结构域(NOD)样受体(NLR)家族Pyrin 域蛋白(NLRP)3 mRNA表达。选择脑损伤程度严重的I- R模型,缺血前15 min于尾静脉注射10、25、50 mg/kg不同剂量HDL,缺血1.5 h和再灌注72 h后处死并取脑损伤组织作TTC染色,检测不同剂量HDL对脑梗死体积的改善作用。酶联免疫吸附试验(ELISA)和qRT- PCR检测大鼠缺血半暗带脑损伤组织中白细胞介素(IL)- 18、IL- 1β和mRNA表达。免疫印迹法检测NLRP3、半胱氨酸天冬氨酸特异性蛋白酶(caspase)- 1表达。 结果 随着I- R时间延长延长,大鼠脑梗死程度加重,神经功能损伤更严重,炎性小体NLRP3 mRNA表达显著上调。中、高剂量HDL治疗对I- R大鼠脑组织有保护作用,可显著降低I- R 72 h后神经功能评分,缩小脑梗死体积,下调脑I- R诱导的IL- 18、IL- 1β和mRNA表达。 结论 HDL可通过抑制NLRP3激活保护脑组织免受I- R损伤,可能为未来缺血性脑卒中治疗提供一新思路。

参考文献/References:

[1] 陈 立, 邹伟婕, 张 宇, 等. miR-29b通过抑制N2a细胞p53凋亡通路减轻氧糖剥夺/再灌注损伤[J]. 介入放射学杂志, 2018, 27: 451-457.
[2] 周腾飞, 朱良付, 李天晓. 影响急性缺血性脑卒中血管内治疗预后的相关因素分析[J]. 介入放射学杂志, 2017, 26: 99-104.
[3] Rathinam VA, Fitzgerald KA. Inflammasome complexes: emerging mechanisms and effector functions[J]. Cell, 2016, 165: 792-800.
[4] 易 敏, 高 荔, 庞 博, 等. NLRP3炎性体加重小鼠脑缺血再灌注损伤的机制探讨[J]. 山东医药, 2014, 54: 7-9.
[5] Mineo C, Deguchi H, Griffin JH, et al. Endothelial and antith-rombotic actions of HDL[J]. Circ Res, 2006, 98: 1352-1364.
[6] Fonarow GC, Smith EE, Saver JL, et al. Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes[J]. Circulation, 2011, 123: 750-758.
[7] Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenoustissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association[J]. Stroke, 2009, 40: 2945-2948.
[8] Dirnagl U, Endres M. Found in translation: preclinical stroke research predicts human pathophysiology, clinical phenotypes,and therapeutic outcomes[J]. Stroke, 2014, 45: 1510-1518.
[9] Martinon F, Bruns K. Tschoopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta[J]. Mol Cell, 2002, 10: 417-426.
[10] Fann DY, Lee SY, Manzanero SA, et al. Pathogenesis of acute stroke and the role of inflammasomes[J]. Ageing Res Rev, 2013, 12: 941- 966.
[11] Fann DY, Lee SY, Manzanero S, et al. Intravenous immuno-globulin suppresses NLRP1 and NLRP3 inflammasome- mediated neuronal death in ischemic stroke[J]. Cell Death Dis, 2013, 4: e790.
[12] Schmidt A, Minnerup J, Kleinschnitz C. Emerging neuroprotective drugs for the treatment of acute ischaemic stroke[J]. Expert Opin Emerg Drugs, 2013, 18: 109-120.
[13] Fann DY, Santro T, Manzanero SA, et al. Intermittent fasting attenuates inflammasome activity in ischemic stroke[J]. Exp Neurol, 2014, 257: 114-119.
[14] Amarenco P, Goldstein LB, Messig M, et al. Relative and cumulative effects of lipid and blood pressure control in the stroke prevention by aggressive reduction in cholesterol levels trial[J]. Stroke, 2009, 40: 2486-2492.
[15] Makihara N, Okada Y, Koga M, et al. Effect of serum lipid levels on stroke outcome after rt-PA therapy: SAMURAI rt-PA registry[J]. Cerebrovasc Dis, 2012, 33: 240-247.
[16] Frias MA, Pedretti S, Hacking D, et al. HDL protects against ischemia reperfusion injury by preserving mitochondrial integrity[J]. Atherosclerosis, 2013, 228: 110-116.
[17] Argraves KM, Gazzolo PJ, Groh EM, et al. High density lipoprotein- associated sphingosine 1- phosphate promotes endothelial barrier function[J]. J Biol Chem, 2008, 283: 25074-25081.

备注/Memo

备注/Memo:
(收稿日期:2018-08-20)
(本文编辑:边 佶)
更新日期/Last Update: 2019-08-21