脑梗死患者外周血单个核细胞Toll样受体及下游信号分子表达与临床预后的相关性研究  

Associations of Toll-like receptors mRNA expressions and their downstream signaling pathways in peripheral blood mononuclear cells with clinical outcomes in patients with cerebral infarction

作　　者：邓玲娜[1] 潘经锐[1] 彭晴霞 董朝飞[1] 王艺东[1] 

机构地区：[1]中山大学孙逸仙纪念医院神经科,广州510120

出　　处：《中华神经医学杂志》2016年第12期1217-1223,共7页Chinese Journal of Neuromedicine

基　　金：广东省自然科学基金（S2013010015209）

摘　　要：目的探讨脑梗死患者外周血单个核细胞Toll样受体（TLRs）及其下游信号分子mRNA表达与临床预后的相关性。方法采用实时荧光定量PCR法测定中山大学孙逸仙纪念医院神经内科自2015年5月1日至2015年12月30日收治的90例前循环脑梗死患者的外周血单个核细胞TLR2、TLR4、TLR3、TLR7、TLR8和TLR9以及下游信号分子Toll样受体相关分子（TRAM）、干扰素调节因子-3（1RF-3）和干扰素-β（IFN-β）的表达，于发病90d时进行改良Rankin量表（mRS）评分，将患者分为结局良好组（mRS≤2分）及结局不良组（mRs〉2分）。通过人组时美国国立卫生研究院卒中量表（Nn-ISS）评分评估病情严重程度，于发病7～14d通过MR／测量脑梗死体积。分析2组患者的TLRs表达、人口信息、危险因素、卒中类型、基线临床信息及影像学检查等，得出和预后良好的相关因素，再进行多因素Logistics回归分析预后的独立危险因素。结果在急性期，结局良好组TLR3、TLR7表达高于结局不良组：在亚急性期，结局良好组仅TLR3表达高于结局不良组，差异均有统计学意义（P〈0．05）。多自变量Logistic回归分析显示，90d结局良好的独立预测因素有：TLR3（OR=4．435，（P=0．001）、CRP（OR=1．12，P=0．033）、人组时NIHSS（OR=1．961，P=0．000）。TLR3、TLR7的表达与NIHSS评分、脑梗死体积呈负相关。IFN-β的表达仅与TLR3表达具有正相关性（r=0．392，P=0．000），且IFN-β表达与IRF-3表达呈正相关（r=0．347，P=0．010）。结论脑梗死患者外周血单个核细胞TLR3mRNA表达与结局良好具有相关性，TLR3可能通过促使抗炎因子IFN-β分泌来介导脑缺血修复作用。Objective To investigate the associations of Toll-like receptors （TLRs） mRNA expressions and their downstream signaling pathways in peripheral blood mononuclear cells with clinical outcomes in patients with cerebral infarction. Methods Ninety patients with cerebral infarction of anterior circulation, admitted to our hospital from May 2015 to December 2015, were chosen. Quantitative real-time PCR was performed to measure the expressions of TLR2, TLR4, TLR3, TLR7, TLR8 and TLR9 and downstream signaling molecules Toll-like receptors related molecule （TRAM）, interferon regulatory factor 3 （IRF-3）, and interferon beta （IFN-β） in peripheral blood mononuclear cells. Good functional outcome was defined as modified Ranldn Scale （mRS） scores〈 2 90 d after onset. National Institutes of Health Stroke Scale （NIHSS） on admission was used to evaluate the severity of stroke, and infarct volume 7-14 d after onset was measured on MR imaging. The baseline characteristics （TLRs, population information, risk factors, stroke types, clinical and imaging data） were compared between patients with good and bad functional outcomes. Multi-factor Logistics regression analysis was performed. Results TLR3 and TLR7 mRNA expressions were correlated with good functional outcome at acute cerebral infarction, and only TLR3 expression was correlated with good functional outcome at sub-acute phase. TLR3 mRNA expression, C-reactive protein （CRP） level, and NIHSS scores on admission were positively correlated with good outcome （OR=4.435, P=0.001; OR=1.12, P=3.033; OR=1.961, P=0.000）. The expressions of TLR3 and IRF-3 were both inversely correlated with NIHSS scores and cerebral infarction volume; IFN-β mRNA expression was positively correlated to TLR3 expression （r=0.392, P=0.000）; IFN-β expression and IRF level were positively correlated （r=0.347, P=0.01）. Conclusion The TLR3 expression is correlated with good functional outcome in peripheral blood mononuclear cells of patients with cerebral infarction,

关 键 词：脑梗死 TOLL样受体 临床预后 TOLL样受体3 干扰素-Β 

分 类 号：R743.33[医药卫生—神经病学与精神病学]