不同潮气量机械通气对急性呼吸窘迫综合征大鼠肺纤维化的作用机制  

Mechanism of mechanical ventilation with different tidal volumes on lung fibrosis in rats with acute respiratory distress syndrome

作　　者：刘海波 张敬敏[1] 刘秀兰 王锋 刘明月 李建玲[1] LIU Haibo;ZHANG Jingmin;LIU Xiulan;WANG Feng;LIU Mingyue;LI Jianling(Department of Anesthesiology,Affiliated Hospital of Chengde Medical College,Chengde 067000,Hebei,China;Department of Anesthesiology,Chengde County Hospital of TCM,Chengde 067000,Heibei,China)

机构地区：[1]承德医学院附属医院麻醉科,承德067000 [2]承德县中医院麻醉科,承德067000

出　　处：《医学研究与战创伤救治》2023年第10期1022-1028,共7页Journal of Medical Research & Combat Trauma Care

基　　金：承德市科学技术研究与发展计划项目(202006A076)。

摘　　要：目的 旨在评估不同潮气量机械通气对急性呼吸窘迫综合征(ARDS)大鼠早期肺纤维化的影响,并初步探讨可能的相关机制。方法 通过尾静脉注射油酸来构建ARDS大鼠模型。对照组(n=10)大鼠给予等量等渗盐水。将建模成功的ARDS模型大鼠根据随机数字表法分为模型组、小潮气量组和大潮气量组,每组10只。采用HE染色和Masson染色评估肺组织损伤和肺组织纤维化。采用酶联免疫吸附实验检测肺组织I型胶原蛋白(COL I)、羟脯氨酸(HYP)和转化生长因子(TGF-β1)的含量。采用蛋白免疫印迹检测核因子类胡萝卜素2相关因子2(Nrf2)信号通路相关蛋白。结果 与对照组相比,模型组大鼠的PaO2/FiO2明显降低,而肺W/D值明显升高(P<0.05)。与模型组相比,小潮气量组和大潮气量组大鼠的PaO2/FiO2和肺W/D值均明显升高(P<0.05)。模型组大鼠的肺组织损伤评分、肺纤维化评分、COL I、Hyp和TGF-β1水平、α-平滑肌肌动蛋白(α-SMA)蛋白表达均明显升高(P<0.05),而E-cadherin、Nrf2、血红素氧合酶-1(HO-1)和醌氧化还原酶-1(NQO-1)蛋白表达均明显降低(P<0.05)。与模型组相比,大潮气量组大鼠的肺组织损伤评分、肺纤维化评分、COL I、Hyp和TGF-β1水平、α-SMA蛋白表达均明显升高(P<0.05),而E-cadherin、Nrf2、HO-1和NQO-1蛋白表达均明显降低(P<0.05)。结论 大潮气量机械通气加重ARDS大鼠的肺组织损伤和早期肺纤维化可能是通过抑制Nrf2信号通路的活化来诱导氧化应激、促进上皮间充质转变来实现。小潮气量机械通气可能更有益于ARDS急性期的治疗。Objective To evaluate the effects of mechanical ventilation with different tidal volumes on early pulmonary fibro-sis in ARDS rats and to preliminarily explore the possible related mechanisms.Methods An ARDS rat model was constructed by tail vein injection of oleic acid.The control group(n=10)rats were given equal amounts of saline.The successfully modeled ARDS model rats were divided into model group,small tidal volume group and large tidal volume group according to the random number table method,with 10 rats in each group.HE staining and Masson staining were used to assess lung tissue injury and lung tissue fibrosis.En-zyme-linked immunosorbent assay was used to detect the levels of lung tissue collagen type I(COL-I),hydroxyproline(HYP)and transfor-ming growth factor(TGF-β1).Protein immunoblotting was used to detect Nrf2 signaling pathway-related proteins.Results Compared with the control group,PaO2/FiO2 was significantly lower and lung W/D values were significantly higher in the model group rats(P<0.05).Compared with the model group,PaO2/FiO2 and lung W/D values were significantly higher in both the small and large tidal volume groups(P<0.05).Lung tissue injury score,lung fibrosis score,COL I,Hyp and TGF-β1 levels,α-SMA protein expression were significantly higher(P<0.05),while E-cadherin,Nrf2,HO-1 and NQO-1 protein expression were significantly lower(P<0.05)in the model group rats.Compared with the model group,the lung tissue injury score,lung fibrosis score,COL I,Hyp and TGF-β1 levels,α-SMA protein expression were significantly higher(P<0.05),while E-cadherin,Nrf2,HO-1 and NQO-1 protein expression were significantly lower(P<0.05)in the rats with large tidal volume.Conclusion Large tidal volume mechanical ventilation can aggravate lung tissue injury and early pulmonary fibrosis in ARDS rats,which may be achieved by inhibiting the activation of Nrf2 signaling pathway to induce oxidative stress and promote epithe-lial-mesenchymal transition(EMT).Small tidal volume mechanical ventilation may be more benefic

关 键 词：急性呼吸窘迫综合征 机械通气 不同潮气量 氧化应激 上皮间质转化 

分 类 号：R445[医药卫生—影像医学与核医学]