国际麻醉学与复苏杂志   2012, Issue (12): 4-4
    
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
王月兰, 宋秀梅, 王慎会, 商丽梅1()
1.山东省千佛山医院
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
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摘要：

目的 丝裂原活化蛋白激酶（mitogen-activated protein kinases，MAP激酶，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250 g～320 g 。采用3％戊巴比妥35 mg/kg～40 mg/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）：① C组（对照组，麻醉后仅做气管切开不做机械通气）；② LV组[正常通气组，潮气量（Vt）: 6 ml/kg，余同过度通气组]；③ HV组[过度通气组，Vt: 40 ml/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（FiO2）21％，通气4 h]；④ SP600125组（SP600125+ HV组，高潮气量通气前30 min给予MAPK拮抗剂SP600125）；⑤ PD98059组（PD98059+ HV组，高潮气量通气前30 min给予MAPK拮抗剂PD98059）；⑥ SB203580组（SB203580+ HV组，高潮气量通气前30 min给予MAPK拮抗剂SB203580）。机械通气4 h后（对照组气管切开后4 h）,采用RT-PCR方法测定肺表面活性蛋白（SP）-A、B、C和RTI40 mRNA表达量。结果 ① 与C组比较，LV组、HV组大鼠肺组织中RTI40表达均增加（P<0.05），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（P>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<0.05），RTI40基因表达降低（P<0.05）。③ SP-A、C基因表达量在PD98059＋HV组较SP600125＋HV组、SB203580＋HV组升高（P < 0.05），④ SP-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RTI40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-induced lung injury，VILI)过程中对肺上皮细胞的分泌功能。
关键词： [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
Abstract:

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 cm H2O. 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 ① 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 inhibited the expressions of the SP-A and SP-C, but upregulated RTI40 gene expressions. The inhibitors of MAPK attenuated the changes of SP-A, C and RTI40 mRNA during the process of high volume ventilation, which indicates that MAPK, at least in part, may play a role in the functions of I and II alveolar epithelial cells in the lung injury induced by mechanical ventilation.
Key words: [Key words] Ventilation induced lung injury; Pulmonary surfactant ; Genes expression;Mitogen-activated protein kinases