丝裂原活化蛋白激酶在机械通气过程中对肺表面活性物质及特异蛋白基因表达的影响  

The effects of mitogen-activated protein kinases on the genes expression of the pulmonary surfactants from alveolar epithelial cells during ventilation induced lung injury in rats

作　　者：宋秀梅[1] 王慎会[1] 商丽梅[1] 王月兰[1] 

机构地区：[1]山东大学附属千佛山医院麻醉科,济南250014

出　　处：《国际麻醉学与复苏杂志》2012年第12期807-810,844,共5页International Journal of Anesthesiology and Resuscitation

基　　金：基金项目：山东省科学厅资助自然基金项目（Y2007C119）

摘　　要：目的丝裂原活化蛋白激酶（mitogen_activatedproteinkinases，MAPK）在机械通气过程中对肺表面活性物质及特异蛋白基因表达的影响和可能机制。方法采用健康成年雄性Sprague-Dawley大鼠48只，体重250g－320g。采用3％戊巴比妥35rag／ks～40mg／kg腹腔注射麻醉后行气管切开置管术，完全随机分组方法分为6组（每组8只）：①C组（对照组，麻醉后仅做气管切开不做机械通气）；②LV组旺常通气组，潮气量（vt）：6ml／kg，余同过度通气组】；③HV组[过度通气组，Vt：40ml／kg，呼吸频率（RR）40次/min，吸呼比（I：E）1：2-1：3，呼气末正压通气（PEEP）=0，吸入氧浓度（Fi02）21％，通气4h]；④SP600125组（SP600125＋HV组，高潮气量通气前30min给予MAPK拮抗剂SP600125）；⑤PD98059组（PD98059＋HV组，高潮气量通气前30min给予MAPK拮抗剂PD98059）；⑥SB203580组（SB203580＋HV组，高潮气量通气前30min给予MAPK拮抗剂SB203580o机械通气4h后（对照组气管切开后4h），采用RT-PCR方法测定肺表面活性蛋白（SP）-A、B、C和RTl40mRNA表达量。结果①与C组比较，LV组、HV组大鼠肺组织中RTl40表达均增加（P〈O．05），而HV组、SP600125＋HV组及SB203580＋HV组肺组织中SP-A、SP-C表达均减少（P〈0．05），LV组中和PD98059＋HV组中的SP-A、C变化均无统计学意义（Jp〉0．05）；②与HV组比较，SP600125＋HV组、PD98059＋HV组、SB203580＋HV组肺组织中SP-A、C基因表达增加（P〈O．05），RTl40基因表达降低（P〈0．05）；③SP-A、C基因表达量在PD98059＋HV组较SP600125＋HV组、SB203580＋HV组升高（P〈0．05）；④SP-B在各组中变化无统计学意义（P〉0．05）。结论高潮气量机械通气致肺上皮细胞特异蛋白SP-A、C基因表达下降和RTl40基因表达上调，而MAPK拮抗剂可以防止该现象发生，提示MAPK影响呼吸机相关性肺损伤（ventilator-inducedlunginjury，VILI）过程中�Objective To investigate the effects of mitogen-activated protein kinases （MAPK） on the genes expression of the pulmonary surfactants from alveolar epithelial cells during ventilation induced lung injury in rats. Methods Anesthetized male SD rats were randomized into six groups： （1） Control group（C） received no mechanical ventilation. （2） Low-volume ventilation（LV） group received mechanical ventilation with Vt=6 ml/kg, RR=40 bmp, I：E=1：2,FiO2=21%, positive end-expiratory pressure = 0. （3） Hyperventilation（HV） group received mechanical ventilation with the same respiratory parameters as the LV group and the Vt was 40 ml/kg. The inhibitors of MAPK including the JNK＇s： SP600125, the ERK＇s： PD98059 and the p38＇s： SB203580 were pretreated 30 min before ventilation just like in the HV group. （4） SP600125 group （SP600125 ＋ HV group）. （5） PD98059 group （PD98059 ＋ HV group）. （6） SB203580 group （SB203580 ＋ HV group）. After 4 h ventilation, the animals in each group were killed and the lungs were removed for detecting the expression of SP-A, B, C and RTI40 mRNA by RT-PCR. Results （i） Compared with group C, the expression of RTI40 mRNA of lung tissue increased significantly in the LV group and the HV group （P〈0.05）, but the expression of SP-A, SP-C mRNA decreased in the HV group,SP600125 group and SB203580 group （P〈0.05）, while there was no significant difference in the expression of SP-A,C mRNA in LV groups and PD98059 group （P〈0.05）. （2） Compared with the HV group, the SP-A, C gene expressions of lung tissue in SP600125 group, PD98059 group and SB203580 group increased significantly （P〈0.05）, but RTI40 gene expressions decreased（P〈0.05）. （3） The SP-A, C gene expressions of lung tissue in PD98059 group increased significantly than those of SP600125 group and SB203580 group. （4） The SP-B gene expression had no difference in all groups. Conclusions The results of our study show that mechanical ventilation

关 键 词：机械通气诱发肺损伤 肺表面活性物质 基因表达 丝裂原活化蛋白激酶 

分 类 号：R614[医药卫生—麻醉学]