【作者】 孙芳；

【导师】 陈美云； 吴可贵；

【作者基本信息】 福建医科大学 ， 内科学， 2006， 硕士

【摘要】 目的应用油酸(oleic acid, OA)静脉注射复制大鼠急性肺损伤(acute lung injury, ALI)模型,探讨肿瘤坏死因子-α(TNF-α)、γ-干扰素(IFN-γ)、白细胞介素-4(IL-4)在油酸性肺损伤中的变化规律;探讨阿奇霉素对OA致ALI大鼠的治疗作用及可能的作用机制,为临床治疗ALI提供一定的理论和实验依据。方法应用OA静脉注射复制大鼠ALI模型。将90只SD大鼠随机分为3组:生理盐水对照组(NC组),油酸致急性肺损伤组(OA组),阿奇霉素治疗组(AZI组)。每组分别在1天、3天、7天抽取动脉血并放血迅速处死。测定动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、pH值及血浆IL-4含量,左上肺测湿/干重比(wet / dry weight,W/D值),下段行病理检查。右肺灌洗,测支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中总蛋白(total proteins,TP)、TNF–α、IFN-γ、IL-4含量,并对BALF中炎症细胞进行分类计数。结果与NC组比较,OA组各时间点W/D值、BALF中的TNF–α、TP及炎症细胞计数显著升高(P <0.01), IFN-γ/IL-4比值、PaO2降低(P <0.01),肺组织病理见充血、水肿、出血、炎性细胞浸润等急性肺损伤表现;AZI组与OA组相比,病理学观察肺组织病变减轻, IFN-γ/IL-4比值、PaO2升高(P <0.05),W/D、TNF-α降低(P <0.05);OA组和AZI组各时间点血浆中IL-4浓度与BALF中IL-4浓度呈正相关(rOA1= 0.857;rOA3=0.841;rOA7= 0.774; r AZI1=0.797;r AZI3=0.830 ;rAZI7=0.829 ,各组P <0.01)。结论(1)ALI病程中存在Th1/ Th2细胞因子失衡,IFN-γ分泌减少,IL-4分泌增加;(2)ALI时,测定血浆中IL-4浓度可以间接反映BALF中IL-4水平;(3)阿奇霉素可以减轻肺微血管渗漏,改善大鼠肺换气功能,降低BALF中TNF-α水平,升高IFN-γ/IL-4比值、恢复Th1优势,部分纠正OA致大鼠肺损伤中Th1/ Th2细胞因子失衡。证实阿奇霉素对ALI有一定的治疗作用。更多还原

【Abstract】 Objective The purpose of this study was to reproduce the model of acute lung injury (ALI) in rats by injecting oleic acid (OA) into the vein, and investigate the alterations of tumour necrosis factor-α(TNF-α),interferon Gamma (IFN-γ), interleukin-4 (IL-4) after ALI induced by OA, and investigate the possible mechanisms of protective effects of azithromycin in OA induced ALI in rats.Methods OA was used to reproduce the model of ALI in rats. 90 adult Sprague-Dawley rats were randomly divided into three groups: normal control group treated by saline injection (NC group),ALI group induced by oleic acid injection (OA group),therapy group treated by oral azithromycin (AZI group).Arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), power of hydrogen (pH) and plasma interleukin-4 level were assayed after the animals were exsanguinated and sacrificed at 1, 3 and 7 days later. The left lung was used to calculate wet / dry weight ratio(W/D)、histopathology, whereas the right lung was lavaged and determined the total proteins(TP)、TNF-α、IFN-γand IL-4 concentration in the bronchoalveolar lavage fluid(BALF), total cell counts and differential analysis in BALF were performed.Results In the OA group, W/D、TNF-α、TP and inflammatory cell counts in the BALF were significantly increased (P <0.01), whereas the ratio of IFN-γ/ IL-4、arterial oxygen tension (PaO2) were significantly decreased(P<0.01) as compared with NC group. Obvious pathological manifestations such as hyperemia、edema、hemorrhage、neutrophil infiltration were shown . In the AZI group, the change of lung pathology was significantly relieved, the ratio of IFN-γ/ IL-4、PaO2 were increased(P <0.05), W/D、TNF-αwere significantly decreased (P <0.05)as compared with OA group. The IL-4 concentrations in the BALF were positively correlated to those in the plasma in the OA and AZI group at the same time point (rOA1= 0.857;rOA3=0.841;更多还原