选择性顺行性脑灌注在猪深低温停循环模型中的脑保护机制  

Neuroprotection of selective antegrade cerebral perfusion on pig model exposed to deep hypothermia circulatory arrest

作　　者：刘子由[1] 梁孟亚[2] 陈光献[2] 唐志贤[1] 荣健[2] 姚尖平[2] 杨潇[2] 吴钟凯[2] 

机构地区：[1]赣南医学院第一附属医院,江西省赣州市341000 [2]中山大学附属第一医院,广州市510080

出　　处：《实用医学杂志》2015年第5期693-696,共4页The Journal of Practical Medicine

基　　金：科技部国家基础研究资助项目(973计划项目)(编号:2010CB5295007);国家自然科学基金资助项目(编号:81460290;81360287);江西省自然科学基金资助项目(编号:2010GZY0031;20142BAB205041);江西省教育厅科技资助项目(编号:GJJ12547;GJJ14695);江西省卫计委资助项目(编号:20155427)

摘　　要：目的:研究TLR4/NF-κB信号通路在深低温停循环(DHCA)脑损伤中的机制及选择性顺行性脑灌注(SACP)对TLR4/NF-κB通路的影响。方法:12只小猪随机分成18℃停循环组(D组,n=6)和18℃选择性顺行性脑灌注组(S组,n=6),处理80 min。ELISA测定血清IL-6,荧光TUNEL和Western blot检测细胞凋亡与NF-κB蛋白,q RT-PCR和Western blot测定TLR4 m RNA及蛋白。结果:S组血清IL-6水平在停循环末和实验终点明显低于D组(P<0.05)。凋亡指数和NF-κB蛋白表达在S组显著降低(P<0.05)。TLR4m RNA和NF-κB/P65蛋白在S组动物的表达较D组显著降低(P<0.05)。结论:TLR4/NF-κB通路在DHCA脑损伤中起重要作用。抑制TLR4/NF-κB通路表达可能是SACP的保护机制。TLR4/NF-κB信号通路可作为DHCA脑保护的新靶点。Objective To explore the expression of TLR4/NF-κB pathway in cerebral injury resulting from DHCA （ deep hypothermia circulatory arrest ） as well as the effect of SACP （ selective antegrade cerebral perfusion）. Methods Twelve pigs were randomly assigned to DHCA group （n = 6） or SACP group （n = 6） at 18 ℃ for 80 min. IL-6 was assayed by ELISA. Apoptosis and NF-κB proteins were detected by fluorescence TUNEL and Western blot, respectively. The level of TLR4 was determined through qRT-PCR and Western blot. Results Serum IL-6 level of SACP group was significantly lower at the end of circulation arrest and experiment and apoptotic index and NF-κB protein were apparently lower in SACP group （P 〈 0.05）. The level of TLR4 protein and mRNA from SACP group decreased significantly （P 〈 0.05）. Conclusions TLR4/NF-κB pathway plays a critical role in pathogenesis of DHCA cerebral injury and attenuating TLR4/NF-κB cytokines probably contributes to neuroprotection of SACP. TLR4/NF-κB pathway may be a novel target for DHCA.

关 键 词：停循环 深低温诱导 选择性顺行性脑灌注 TLR4 NF-ΚB IL-6 脑损伤 

分 类 号：R-332[医药卫生] R651.15