磷脂酰肌醇3-激酶在油酸型急性肺损伤大鼠肺内的表达及其意义

Expression of phosphoinositide 3 kinase in rats with acute lung injury induced by oleic acid

目的研究磷脂酰肌醇3-激酶(PI3-K)在油酸型急性肺损伤大鼠肺内的表达情况及其与肺组织细胞凋亡的关系。方法健康雄性SD大鼠60只,随机分为5组,每组12只油酸组共4组,分别在尾静脉注入油酸0.25ml/kg后1h,2h,4h,24h颈总动脉放血处死,对照组尾静脉注入生理盐水0.25ml/kg,2h颈总动脉放血处死。观察各组动脉血气、左肺湿/干比、肺系数、BALF中蛋白含量、肺通透指数,免疫组化法测定肺内Fas-L表达,免疫组化法和免疫印迹法测定肺内PI3-K蛋白表达。结果油酸组大鼠PaO2明显降低,左肺湿/干比、肺系数、BALF中蛋白含量及肺血管通透性明显增高(P<0.01),支气管、肺泡上皮细胞,肺血管内皮细胞,肺泡巨噬细胞上表达PI3-K和Fas-L明显增多(P<0.01),且PI3-K表达峰值时间早于Fas-L。结论Fas-L依赖的肺泡上皮细胞、肺血管内皮细胞和巨噬细胞凋亡参与早期ALI发病机制,此过程可能通过PI3-K信号转导通路予以实现。

Objective To study the expression of phosphoinositide 3 kinase （PI3-K） and its relationship with lung cell apoptosis in rats with acute lung injury induced by oleic acid. Methods 60 healthy male SD rats were divided into 5 groups randomly, with 12 rats for each group. 0. 25ml/kg oleic was injected into the tail vein in 4 oleic groups in which the rats were respectively sacrificed after lh, 2h, 4h, 6h and 24h by exsanguination. In the control group 0. 25ml/kg of saline was injected intravenously and sacrificed 2h later. Arterial blood gas, left lung wet/dry ratio, lung index, protein content of BALF, and pulmonary permeability index （PPI） were determined. Fas-L expression of lung tissue was determined by immunohistochemical method and protein expression of PI3-K was determined by We.stem blot and immunohistochemical method. Results PaO2 was lowered, and left lung wet/dry ratio, lung index, and protein content of BALF and PPI were increased obviously after oleic acid injection. Fas-L and PI3-K in bronchus epithelial cells, alveolar epithelial cells, pulmonary vessel endo- thelial cells and macrophage cells were highly expressed in the lung of ALl rats, and peak value of PI3-K appeared earlier than Fas-L. Conclusion Fas-L related apoptosis of bronchial epithelial cells, alveolar epithelial cells, pulmonary vessel endothelial cells and macrophage cells participated in the pathogenesis of earlier period of ALI through PI3-K transduction pathway.