气道内高压力促进3种气道重塑相关因子的表达

High pressure level in human airway enhances the expression of 3 cytokines related to airway remodeling

目的探讨机械通气情况下气道内不同压力水平对气道重塑相关因子表达的影响。方法手术室经全麻行机械通气的42例慢性阻塞性肺疾病(COPD)作为COPD组和33例无基础肺疾病患者作为对照组。机械通气根据吸气峰压(PIP)水平又分为高、中、低压力组(分别为24、22和20 cm H_2O),呼气末正压均为5 cm H_2O。机械通气前及3 h后收集支气管肺泡灌洗液(BALF)。酶联免疫吸附法和Western blot法检测BALF中气道重塑相关因子成纤维生长因子2(FGF-2)、转化生长因子-β1(TGF-β1)和基质金属蛋白酶-9(MMP-9)蛋白表达水平。结果 1)机械通气前COPD组BALF中的FGF-2、TGF-β1和MMP-9蛋白水平明显高于对照组(P<0.01)。2)机械通气后对照组在高压力刺激下FGF-2、TGF-β1和MMP-9表达水平升高(P<0.05);而COPD组压力刺激下上述3种蛋白表达升高更明显(P<0.05),且高压力组>中及低压力组(P<0.05)。3)相关性分析显示,COPD组BALF中FGF-2、TGF-β1、MMP-9表达水平与气道压力成正相关(P<0.01)。结论机械通气时气道内的持续高压力可能通过作用于气道上皮细胞内压力敏感通道进而提高气道重塑因子FGF-2、TGF-β1、MMP-9的表达水平,COPD患者尤为显著。

Objective To explore the relationship between different airway pressure and expression of related cyto- kines to airway remodeling. Methods Fourty-two chronic obstructive pulmonary disease cases （ COPD group） and thirty-three control cases were collected. The above cases underwent mechanical ventilation in the period of general anesthesia. According to different levels of peak inspiratory pressure （PIP） , above two groups, randomly and respectively, were divided into high PIP （HPIP, 24 cmH2O） group, moderate PIP （MPIP, 22 cmH2O） group, low PIP （LPIP, 20 cmH2O） group. All positive end expiratory pressure （PEEP） was set to 5 cmH2O. Then the collection of BALF was performed before and 3 hours after applying ventilator. The related factors to airway remodeling, such as fibroblast growth factor 2 （FGF-2）, transforming growth factor β1 （TGF-β1） and matrix metalloproteinase-9 （MMP-9）, were measured by enzyme-linked immunosorbent assay （ELISA） and Western blot. Results 1 ）Before mechanical ventilation, the levels of FGF-2, TGF-β1 and MMP-9 in COPD group were higher than control group （P 〈 0.01 ）. 2） 3 hours after mechanical ventilation, we saw significant upregulated expression of FGF-2, TGF-β1, MMP-9 in HPIP subgroup in control group （P 〈0. 05） and the 3 factors levels of COPD group were all increased （P 〈 0. 05 ）. Moreover, HPIP subgroup was significantly higher than MPIP and LPIP subgroup in COPD group （P 〈 0. 05 ）. 3 ）The expression of FGF-2, TGF-β1, MMP-9 in BALF had a positive correlation with the airway pressure levels in COPD group （P 〈 0. 01 ）. Conclusions Under mechanical ventilation, sustained high airway pressure may enhance the expression of FGF-2, TGF-β1 and MMP-9 which may result in airway remodeling by mechanosensitive cation channel in bronchial epithelial cells, especially in COPD patients.