EGFR-p38 MAPK信号通路参与机械通气肺损伤大鼠肺组织HMGB1的表达  

EGFR-p38 MAPK signaling pathway is involved in expression of HMGB1 in pulmonary tissues of rats with ventilator-induced lung injury

作　　者：唐春林[1] 丁宁[2] 程傲冰[2] 

机构地区：[1]广州医学院附属肿瘤医院麻醉科,广东广州510095 [2]广州市第一人民医院麻醉科,广东广州510180

出　　处：《中国病理生理杂志》2013年第6期1029-1033,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81272136);广东省科技计划项目(No.2010B031600011);广东省医学科研基金资助项目(No.A2012278);广州市科技计划重点项目(No.2012J4100034);广州市医药卫生科技重点项目(No.20121A021001)

摘　　要：目的:研究表皮生长因子受体(epidermal growth factor receptor,EGFR)-p38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路在机械通气肺损伤(ventilator-induced lung injury,VILI)大鼠肺组织高迁移率族盒蛋白1(high mobility group box 1 protein,HMGB1)表达中的作用。方法:健康SD大鼠32只随机分为4组:对照组(A组)不行机械通气,保留自主呼吸;小潮气量通气组(B组)潮气量(VT)为8 mL/kg;大潮气量通气组(C组)VT为40 mL/kg;大潮气量通气+EGFR拮抗剂AG-1478组为D组。机械通气4 h后处死动物,测定支气管肺泡灌洗液中总蛋白水平、白细胞计数以及肺湿干重比值(W/D)和髓过氧化物酶(MPO)活性,采用HE染色观察肺组织病理学改变,Western blotting方法检测肺组织磷酸化EGFR、磷酸化p38和HMGB1蛋白表达,RT-PCR方法检测EGFR mRNA的表达。结果:通气4 h后,与A组比较,C组肺组织病理学改变明显,总蛋白水平、白细胞计数、肺W/D、MPO活性、EGFR mRNA表达和磷酸化水平、p38磷酸化水平以及HMGB1蛋白表达均显著增加(P<0.05);与C组比较,D组上述各项指标的变化均显著降低(P<0.05)。结论:大潮气量机械通气可引起大鼠急性肺损伤,其机制可能与通过EGFR-p38 MAPK信号通路介导HMGB1蛋白的表达有关。AIM： To investigate the role of epidermal growth factor receptor （EGFR）-p38 mitogen-activated protein kinase （MAPK） pathway in the expression of high mobility group box 1 protein （ HMGB1 ） in the lung tissues of rats with ventilator-induced lung injury （VILI）. METHODS： Thirty-two healthy Sprague-Dawley （SD） rats were randomly divided into 4 groups （ n = 8 each） ： group A, spontaneous breathing; group B, small tidal volume ventilation （ VT= 8 mL/ kg） ; group C, high tidal volume ventilation （VT =40 mL/kg） ; group D, high tidal volume ventilation plus EGFR antago- nist AG-1478. The rats in group B, group C and group D were mechanically ventilated for 4 h and then all animals were sacrificed. Total protein content and white blood cell （WBC） count in bronchoalveolar lavage fluid （BALF）, the lung wet/ dry weight ratio （W/D） and myeloperoxidase （MPO） activity were determined. The histological changes of lung tissues were observed by HE staining. The EGFR protein and mRNA expression, p38 MAPK activity and HMGB1 protein expres- sion in the lung tissues were also detected. RESULTS： The inflammatory responses as evidenced by lung HE staining, to- tal protein and WBC in BALF, the lung W/D and MPO activity were significantly higher in group C than those in group A （P 〈 0. 05）. The mRNA expression of EGFR, EGFR activity, p38 activity and HMGB1 protein level also significantly in- creased in group C （P 〈 0. 05） as compared with group A. Significant decreases in the above indexes in group D were ob- served as compared with group C. CONCLUSION： High tidal volume ventilation induces acute lung injury, which may be related to up-regulation of HMGB1 expression through EGFR-p38 MAPK signal pathway.

关 键 词：机械通气 急性肺损伤 受体 表皮生长因子 高迁移率族盒蛋白1 丝裂原激活蛋白激酶类 

分 类 号：R563.8[医药卫生—呼吸系统]