TLR4/NF-κB通路在深低温停循环逆行脑灌注技术脑保护机制中作用的研究  

The role of TLR4/NF-κB pathway in cerebral protective effect of retrograde cerebral perfusion during deep hypothermic circulatory arrest

作　　者：梁孟亚[1] 唐志贤[1] 陈光献[1] 荣健[1] 戴刚[1] 吴钟凯[1] 

机构地区：[1]中山大学附属第一医院心脏外科,广州510080

出　　处：《中华临床医师杂志（电子版）》2013年第19期82-85,共4页Chinese Journal of Clinicians(Electronic Edition)

基　　金：科技部国家基础规划"973"项目(2010CB5295007)

摘　　要：目的研究TLR4/NF-κB通路是否参与深低温停循环逆行脑灌注的脑保护机制。方法五指山小型猪共10头,随机分成单纯深低温停循环组(DHCA组,n=5)与深低温停循环逆行脑灌注组(RCP组,n=5)。建立体外循环后,DHCA组降温至18℃后停循环40 min,RCP组停循环后经上腔静脉以10 ml/kg流量逆行脑灌注40 min。定期抽血检测血清IL-6水平。复灌180 min后处死动物取脑皮质组织行HE染色,Western blotting检测脑皮质TLR4,NF-κB/p65蛋白表达。结果脑皮质HE染色显示DHCA组较RCP组有更多炎症细胞浸润。在复灌60 min,复灌120 min及复灌180 min三个时点RCP的IL-6水平均显著低于DHCA组(t=7.314,P<0.01;t=5.172,P<0.01;t=4.676,P<0.01)。复灌180 min后RCP组脑皮质中TLR4水平明显低于DHCA组(t=10.212,P<0.001)。复灌180 min后RCP组脑皮质中NF-κB/p65水平明显低于DHCA组(t=3.344,P=0.011)。结论 RCP通过抑制TLR4/NF-κB信号通路而发挥抗炎作用,这可能是RCP脑保护作用的机制之一。Objective To investigate whether TLR4/NF-r,_B Pathway is involved in cerebral protective effect of retrograde cerebral perfusion（RCP） during deep hypothermic circulatory arrest （DHCA）. Methods Ten piglets of either sex （weigh 7.5-17.4 kg） were randomly assigned to 40 rain of circulatory arrest （CA） at 18℃ without cerebral perfusion （DHCA group, n=5） or RCP （RCP group, n=5）. Blood samples were collected for assessment of serum IL-6 levels. After 3 h of reperfusion, cortical tissue was harvested for HE staining, western blotting of TLR4 and NF-kB/p65 expression. Results More severe inflammatory response was observed in brain tissue of DHCA group than RCP group. Serum IL-6 levels were significantly higher in the DHCA group than in RCP groups at 60 min, 120 min and 180 min after reperfusion （t=7.314, P〈0.01; t=5.172, P〈0.01; t= 4.676, P〈0.01 respectively）. After 40 rain of CA, TLR4 expression was significantly lower in RCP animal＇s cortex than those in the DHCA group （t= 10.212, P〈0.001）; also lower NF-kB/p65 expression was found in RCP group than those in DHCA group（t=3.344, P=0.011）. Conclusion One possible mechanism of cerebral protective effect of RCP is to inhibit the expression of TLR4/NF-r,B Pathway.

关 键 词：停循环 深低温诱导 炎症 TOLL样受体 逆行脑灌注 

分 类 号：R654.1[医药卫生—外科学]