紫杉醇诱发肺损伤的机制及帕瑞昔布钠的干预作用  

Mechanism of Paclitaxel-induced Lung Injury and Preventive Role of Parecoxib

作　　者：刘文杰[1] 林文前[1] 李慧婷[1] 张天华[1] 操隆辉[1] 

机构地区：[1]华南肿瘤学国家重点实验室//中山大学肿瘤防治中心麻醉科,广东广州510060

出　　处：《中山大学学报（医学科学版）》2013年第3期407-414,共8页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(S2011010004049)

摘　　要：【目的】探讨紫杉醇诱发大鼠肺损伤的机制及帕瑞昔布钠的干预作用。【方法】实验大鼠随机分为4组:空白对照组(Con组),紫杉醇化疗组(Pac组),帕瑞昔布钠干预组(Pac+Pare组),帕瑞昔布钠组(Pare组)。观察肺泡换气功能、肺泡-毛细血管膜通透性及肺组织病理的改变,检测肺组织炎性因子、环氧化酶2(COX-2)含量及紧密连接蛋白(ZO-1及Claudin-4蛋白)的表达。【结果】与Con组比较,Pac组大鼠肺组织COX-2表达显著升高(P<0.01),肺组织炎性改变明显;ZO-1及Claudin-4蛋白表达减少(P<0.01);肺泡-毛细血管膜通透性增高(P<0.01),肺换气功能减低。Pac+Pare组、Pare组与Con组比较,上述各指标差异无统计学意义。【结论】紫杉醇可损伤大鼠肺泡-毛细血管屏障,其机制可能是紫杉醇引起肺组织COX-2过表达,继而激活炎症级联反应损伤肺泡毛细血管膜上的屏障结构—紧密连接;而COX-2特异性抑制剂帕瑞昔布钠干预可阻断此损伤。[ Objective ]To investigate the mechanism of paclitaxel-induced lung injury and the preventive role of parecoxib in rats. [ Methods] 28 Wistar rats were randomly assigned into four groups： Control group, Paclitaxel group, Paclitaxe＋Parecoxib group, and Parecoxib group. The changes of pulmonary permeability, gas exchange of alveolar capillary membrane and pathological section were examined. Inflammatory cytokine in lung tissue and the content of COX-2, protein expression of tight junction were detected. [Results ] Compared with the Control group, the Pac group has a significant increase in COX-2 expression, ICAM-1, neutrophils counts and decrease in ZO-1, Clandin-4 protein in lung tissue. Pulmonary permeability in Paclitaxel group was increased and gas exchange dysfunction developed. There were no statistical differences among Paclitaxe＋Parecoxib group, Parecoxib group and Control group. [Conclusion] Paclitaxel chemotherapy injury alveolar capillary barrier in rats. The possible mechanism was that Paclitaxel can cause Cox-2 overexpression, which activated lung inflammatory reaction and damaged the tight junction protein of alveolar capillary membrane. However, the Cox-2 specific inhibitor parecoxib can protect lung from these injuries.

关 键 词：肺损伤 肺泡-毛细血管屏障 紫杉醇 COX-2 紧密连接 

分 类 号：R619.9[医药卫生—外科学]