【摘要】 目的初步探讨Toll样受体4(TLR4)在创伤后急性肺损伤(ALI)发病机制中的作用及临床意义。方法将48例创伤后ALI患者(ALI组)分为多器官功能障碍综合征(MODS)亚组(27例)和非MODS亚组(21例),再根据随访结果分为存活亚组(35例)和死亡亚组(13例);另选择12名健康体格检查者作为对照组。应用反转录-聚合酶链反应及流式细胞术检测对照组及ALI组确诊当天及确诊后第3、7天的外周血单核细胞TLR4 mRNA及蛋白表达,于确诊当天采用酶联免疫吸附试验检测ALI组血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-I、IL-6水平,并进行肺损伤评分和急性生理和慢性健康评分(APACHEⅡ评分)。结果对照组的外周血单核细胞TLR4 mRNA及蛋白表达均显著低于ALI组各时间点(P值分别<0.01或0.05)。ALI组确诊第3天的外周血单核细胞TLR4 mRNA及蛋白表达均显著高于确诊当天(P值均<0.05);确诊第7天的TLR4 mRNA及蛋白表达有下降趋势,但与确诊当天及确诊第3天的差异均无统计学意义(P值均>0.05)。MODS亚组各时间点外周血单核细胞TLR4 mRNA及蛋白表达均显著低于非MODS亚组(P值均<0.05),死亡亚组各时间点TLR4 mRNA及蛋白表达均显著低于存活亚组(P值均<0.05)。ALI患者确诊当天外周血单核细胞TLR4蛋白表达与血清IL-1及TNF-α水平、肺损伤评分、氧合指数呈正相关(r值分别为0.348 1、0.407 2、0.291 0、0.423 7,P值均<0.05)。结论 TLR4可能参与创伤后ALI的发生、发展,且对这类患者的病情发展及转归有一定的预测作用。更多还原

【Abstract】 Objective To explore the role of Toll-like receptor 4（TLR4） in acute lung injury（ALI） induced by trauma.Methods Totally 48 patients with traumatic ALI in the intensive care unit（ICU） were divided into multiple organ dysfunction syndrome（MODS） group and non-MODS group according to the MODS diagnostic criterion.They were followed up for 28 d and then assigned to survival group and death group.Twelve healthy people were enrolled in the control group.The expression of TLR4 mRNA and TLR4 protein in the monocytes of peripheral blood was measured by real-time polymerase chain reaction（RT-PCR） and flow cytometry, respectively,at 24 h,the 3^rd and 7^th day after diagnosis.The concentration of tumor necrosis factor（TNF）-α, interleukin(IL>-1 and IL-6 in the ALI patients were detected by enzyme-linked immunosorbent assay（ELISA） at 24 h after diagnosis.Lung injury scores and acute physiological and chronic health evaluation II（APACHE II） scores were calculated at the same time.Results The expression levels of TLR4 mRNA and TLR4 protein in the healthy adults were significantly lower than those in the ALI patients at all time points（P<0.01 or 0.05）.As compared with the 1^st day,the expression of TLR4 mRNA and TLR4 protein on the 3^rd day in the ALI patients was significantly increased（all P<0.05）,while the expression tended to decrease on the 7^th day and there was no statistical difference（P > 0.05）.The expression levels of TLR4 mRNA and TLR4 protein in the MODS group were significantly lower than those in non-MODS group（P<0.05）.The expression levels of TLR4 mRNA and TLR4 protein in the death group were also significantly lower than those in the survival group（P<0.05）.The expression of TLR4 protein was positively correlated with TNF-α（r = 0.348 1）,IL-1（r = 0.407 2）,lung injury scores（r = 0.291 0） and p_aO₂/FiO₂（r = 0.423 7） when the ALI was diagnosed（all P<0.05）.Conclusion TLR4 may participate in the development and progression of traumatic ALI and can be used to evaluate the state of illness and prognosis.更多还原