体外膈肌起搏联合高压氧处理对呼吸机相关膈肌功能障碍的影响  

Effect of external diaphragm pacing combined with hyperbaric oxygen therapy on ventilator-induced diaphragm dysfunction

作　　者：李冰 陈文豪 刘培 李惠萍 陶维华 张红璇[3] Li Bing;Chen Wenhao;Liu Pei;Li Huiping;Tao Weihua;Zhang Hongxuan(Respiratory Intensive Care Unit,Shenzhen Institute of Respiratory Disease,Shenzhen People’s Hospital(The Second Clinical Medical College of Jinan University),Shenzhen 518020,China;Hyperbaric Oxygen Therapy Department,Shenzhen People’s Hospital(The Second Clinical Medical College of Jinan University),Shenzhen 518020,China;Institute of Gerontology(Physical Examination Center),Guangdong Provincial People’s Hospital,Guangzhou 510080,China)

机构地区：[1]深圳市人民医院(暨南大学第二临床医学院)呼吸疾病研究所,呼吸与危重症医学科,深圳518020 [2]深圳市人民医院(暨南大学第二临床医学院)高压氧生物处理科,深圳518020 [3]广东省人民医院老年医学研究所,广东省干部体检中心,广州510080

出　　处：《中华航海医学与高气压医学杂志》2022年第2期177-183,220,共8页Chinese Journal of Nautical Medicine and Hyperbaric Medicine

基　　金：广东省卫生健康委员会医学科研基金项目(A2021058)。

摘　　要：目的探讨体外膈肌起搏(EDP)联合高压氧(HBO)处理对呼吸机相关膈肌功能障碍(VIDD)的保护性作用及其机制。方法将100只健康雄性大鼠按随机数字表法分为空白对照组(BC组)、模型组(VIDD组)、体外膈肌起搏组(EDP组)、高压氧处理组(HBO组)和联合处理组(EDP+HBO组, 体外膈肌起搏的同时给予高压氧处理), 每组20只。气管切开后给予控制性机械通气建立VIDD大鼠模型, VIDD组不进行干预, 其余各组给予相应的处理。连续处理10 d后取材, 检测膈肌重量(DW)及膈肌重量/体重比(DW/BW)、离体膈肌收缩力、肌纤维横截面积变化情况及膈肌相关因子的表达水平。结果与BC组比较, VIDD组DW、DW/BW及肌纤维横截面积下降, 膈肌纤维结构损伤明显, 离体膈肌收缩力显著下降;膈肌组织中肌球蛋白重链-1(MHC-1)、Kelch样环氧氯丙烷相关蛋白-1(Keap1)、线粒体动力相关蛋白1(Drp1)、肌肉萎缩蛋白Fbox-1(atrogin-1)、肌肉环状指蛋白-1(MuRF-1)、半胱氨酸天冬氨酸蛋白酶-3(caspase-3)、自噬相关蛋白(beclin1)明显升高(P<0.05), 肌球蛋白重链-2(MHC-2)、核因子E2相关因子2(Nrf2)、磷酸化蛋白激酶B(p-Akt)、线粒体融合蛋白-2(Mfn2)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)表达水平明显下降(P<0.05)。与VIDD组比较, EDP+HBO组DW、DW/BW增高[(0.35±0.02)gvs.(0.63±0.06)g, (0.78±0.08)×10^(3)vs.(1.34±0.06)×10^(3), 均P<0.05], 膈肌纤维结构损伤明显改善, 肌纤维横截面积明显增加[(2 235.33±142.58)μm^(2) vs(4 564.82±406.72)μm^(2), P<0.05], 离体收缩力显著增强[(1.15±0.42)N/cm^(2)vs.(2.19±0.10)N/cm^(2), P<0.05], 膈肌标本中MHC-1、Keap1、Drp1、atrogin-1、MuRF-l、caspase-3、beclin1表达逐渐下降, MHC-2、p-Akt、Mfn2、Nrf2、SOD、GSH-Px表达水平明显升高, 膈肌功能改善最明显, 差异有统计学意义(P<0.05)。结论体外膈肌起搏联合高压氧处理能显著增加膈肌收缩力、减轻氧化应激反应�Objective To investigate the protective effect of external diaphragm pacing(EDP)combined with hyperbaric oxygen(HBO)therapy on preventing ventilator-induced diaphragm dysfunction(VIDD)and its related mechanism.Methods A total of 100 adult male rats were randomly divided into five groups:blank control(BC)group,VIDD group,EDP group,HBO therapy group,and the combination of EDP and HBO therapy(EDP+HBO)group,with 20 rats per group.After tracheotomy,the BC group received no treatment,while the rats in the other four groups were given controlled mechanical ventilation to establish the VIDD rat model.And after successful modeling,the VIDD group did not receive further intervention,and the other three groups were treated accordingly.After 10 days of consecutive treatment,the changes in diaphragm weight(DW)and DW/body weight(BW),contraction force of diaphragm in vitro,and transection area of muscle fibers of each group were measured.Gene and protein expressions of diaphragm-related factors were detected.Results Compared with the BC group,the DW,DW/BW,the transection area of muscle fibers,and the fiber structure and the contraction force of diaphragm in vitro of the VIDD group were decreased significantly.The expression levels of MHC-1,Keap1,Drp1,atrogin-1,MuRF-l,caspase-3,and beclin1 in the VIDD group were significantly increased while the expression levels of MHC-2,p-Akt,Mfn2,Nrf2,SOD,and GSH-Px were significantly decreased after treatment(P<0.05).Compared with the VIDD group,the EDP+HBO group had higher DW and DW/BW[(0.35±0.02)g vs.(0.63±0.06)g,0.78±0.08 vs.1.34±0.06,both P<0.05],stronger contraction force of diaphragm in vitro[(1.15±0.42)N/cm^(2)vs.(2.19±0.10)N/cm^(2),P<0.05],declining expression levels of MHC-1,Keap1,Drp1,atrogin-1,MuRF-l,caspase-3,and beclin1,increased expression levels of MHC-2,p-Akt,Mfn2,Nrf2,SOD,and GSH-Px,and much better diaphragmatic function,and all the differences were statistically significant(P<0.05).Conclusion External diaphragm pacing combined with HBO therapy can significantly mitiga

关 键 词：呼吸机相关膈肌功能障碍 体外膈肌起搏 高压氧 机械通气 大鼠 

分 类 号：R565[医药卫生—呼吸系统]