文章摘要
单肺通气时非通气侧肺持续中低流量给氧在老年患者肺癌根治术中的应用
Application of continuous low-and medium-flow oxygen in non-ventilated lung on ferroptosis of alveolar macrophage during radical lung cancer in elderly patients
  
DOI：10.12089/jca.2021.09.002
中文关键词: 肺通气  肺泡巨噬细胞  肺损伤  铁死亡  老年
英文关键词: Lung ventilation  Alveolar macrophages  Lung injury  Ferroptosis  Aged
基金项目:河南省医学科技攻关计划-联合共建项目（2018020564）
作者单位E-mail
张洪军 471003,河南科技大学临床医学院,河南科技大学第一附属医院麻醉科  
苗亚飞 471003,河南科技大学临床医学院,河南科技大学第一附属医院麻醉科  
刘相乐 471003,河南科技大学临床医学院,河南科技大学第一附属医院麻醉科  
麻黎斯 471003,河南科技大学临床医学院,河南科技大学第一附属医院麻醉科  
司建洛 471003,河南科技大学临床医学院,河南科技大学第一附属医院麻醉科 yxy_2018@tom.com 
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中文摘要:
      
目的 探讨单肺通气(OLV)时非通气侧肺持续中低流量给氧对老年患者肺癌根治术中肺泡巨噬细胞(AM)铁死亡的影响。
方法 选择2019年12月至2020年8月择期行胸腔镜下肺癌根治术的老年患者60例,男31例,女29例,年龄65~80岁,BMI 18~25 kg/m2,ASA Ⅱ或Ⅲ级。采用随机数字表法将患者分为两组：观察组和对照组,每组30例。OLV时观察组非通气侧肺给予1~4 L/min持续性中低流量给氧,对照组非通气侧肺不给予持续性中低流量给氧。于术前(T0,基础值)、麻醉诱导后即刻(T1)、OLV后30 min (T2)、1 h (T3)、2 h (T4)采集桡动脉血并测定SpO2、PaO2和PaCO2,计算氧合指数(OI=PaO2/FiO2)。记录术前一秒用力呼气容积(FEV1)/用力肺活量(FVC)比值。T3时采集支气管肺泡灌洗液(BALF),采用流式细胞术分选AM,比色法测定AM内FE2+、丙二醛(MDA)浓度和超氧化物歧化酶(SOD)活性,Western blot法检测AM内长链脂酰辅酶A合成酶4(ACSL4)及谷胱甘肽过氧化物酶4(GPX4)蛋白含量。T3时切取肺癌周边正常肺组织,采用HE染色,光镜下观察肺组织病理学并进行肺组织损伤评分。记录PACU停留时间和住院时间,记录肺部并发症以及呼吸抑制、窦性心动过缓、窦性心动过速、高血压、低血压、恶心呕吐等不良事件发生情况。
结果 与T0时比较,两组T1—T4时SpO2明显升高(P<0.05),T1时PaCO2明显降低(P<0.05)；对照组T1和T3时PaO2明显升高(P<0.05),T2—T4时PaCO2明显升高(P<0.05),T1时OI明显升高(P<0.05),T2—T3时OI明显降低(P<0.05)；观察组T1—T4时PaO2明显升高(P<0.05),T3时PaCO2明显降低(P<0.05),T1、T3、T4时OI明显升高(P<0.05)。与对照组比较,观察组T2—T4时SpO2、PaO2和OI明显升高(P<0.05),PaCO2明显降低(P<0.05)；T3时肺损伤评分明显降低(P<0.05),AM内FE2+、MDA浓度明显降低(P<0.05),SOD活性明显升高(P<0.05),ACSL4蛋白含量明显降低(P<0.05),GPX4蛋白含量明显升高(P<0.05)；术后住院时间明显缩短(P<0.05),肺部并发症发生率明显降低(P<0.05)。两组PACU停留时间以及不良事件发生率差异无统计学意义。对照组肺泡壁增厚、水肿,可见大量中性粒细胞和单核细胞,肺泡腔内可见较多炎性渗出,肺间质明显增生可见大量炎性细胞浸润。观察组肺泡间隔增宽,毛细血管未见明显充血,小部分肺泡腔可见红细胞及炎性渗出液,肺间质炎性细胞浸润明显减少。
结论 老年患者胸腔镜下肺癌根治术中非通气侧肺持续中低流量给氧可减轻非通气侧肺损伤,其机制可能与抑制AM铁死亡有关。
英文摘要:
      
Objective To investigate the effects of continuous low-and medium-flow oxygen in non-ventilated lung on ferroptosis of alveolar macrophage during radical lung cancer in aged patients.
Methods Sixty patients undergoing thoracoscopic radical resection of lung cancer from December 2019 to August 2020, 31 males and 29 females, aged 65-80 years, BMI 18-25 kg/m2, ASA physical status Ⅱ or Ⅲ, were divided into observation group and control group according to the random number table method, 30 patients in each group. After one-lung ventilation, the observation group was given continuous low-to-medium flow oxygen at 1-4 L/min to the non-ventilated side lungs, while the control group was not given continuous low-to-medium flow oxygen to the non-ventilated side lungs. Radial arteries were collected before surgery (T0, base line), immediately after induction of anesthesia (T1), 30 minutes (T2), 1 hour (T3) and 2 hours (T4) after OLV, SpO2, PaO2 and PaCO2 were measured, and oxygenation index (OI = PaO2/FiO2) was calculated. The ratio of forced expiratory volume (FEV1) / forced vital capacity (FVC) in one second before operation, general conditions and operation related conditions of patients were recorded. Bronchoalveolar lavage fluid (BALF) was collected at T3 and AM was sorted by flow cytometry. Colorimetric method was used to determine the concentration of FE2+, MDA and SOD activity in AM, and Western blot was used to detect the expression of long-chain acyl-CoA synthase 4 (ACSL4) and glutathione peroxidase 4 (GPX4) in AM. Normal lung tissues around the lung lobe to be resected were excised, and the pathological changes of the lung tissue were observed under a light microscope using HE staining and the lung injury score was performed at T3. The stay time of postanesthesia car unit (PACU), hospital stay and the incidence of pulmonary complications and major adverse events before discharge such as respiratory depression, sinus bradycardia, sinus tachycardia, hypertension, hypotension, nausea and vomiting were also recorded.
Results Compared with T0, SpO2 in the two groups was increased significantly at T1-T4 (P < 0.05), PaCO2 in the two groups was decreased significantly at T1(P < 0.05), PaO2 in the control group was increased significantly at T1 and T3 (P < 0.05), PaCO2 in the control group was significantly increased at T2-T4(P < 0.05), OI in the control group was significantly increased at T1(P < 0.05), OI in the control group was significantly decreased at T2-T3 (P < 0.05), PaO2 in the observation group was increased significantly at T1-T4 (P < 0.05), PaCO2 in the observation group was significantly decreased at T3 (P < 0.05), and OI in the observation group was significantly increased at T1, T3, and T4 (P < 0.05). Compared with the control group, SpO2, PaO2 and OI in the observation group were increased significantly (P < 0.05), while PaCO2 was decreased significantly at T2-T4 (P < 0.05). Compared with the control group, the lung tissue injury score at T3 was significantly decreased in the observation group (P < 0.05). Compared with the control group, the concentration of FE2+ and MDA in AM in the observation group was decreased (P < 0.05), the activity of SOD was increased (P < 0.05), and the expression of ACSL4 was decreased and GPX4 was increased (P < 0.05) in the observation group. Compared with the control group, the incidence of pulmonary complications before discharge was significantly lower (P < 0.05), and the stay time of postoperative hospital was significantly shorter (P < 0.05) in the observation group. There was no significant difference in the duration of PACU and the incidence of adverse events between the two groups. In the control group, the alveolar walls were thickened and edema, and a large number of neutrophils and monocytes were displayed. There were more inflammatory exudates in the alveolar cavity, and a large number of inflammatory cell infiltrations were seen in the pulmonary interstitial hyperplasia. In the observation group, the alveolar compartment was widened, the capillaries were not significantly congested, red blood cells and inflammatory exudate were seen in a small part of the alveolar cavity, and the inflammatory cell infiltration in the lung interstitium was significantly decreased.
Conclusion Continuous low and medium flow oxygen in non-ventilated lung during thoracoscopy radical lung cancer surgery in elderly patients can reduce non-ventilated side lung injury, and the mechanism may be related to the inhibition of ferroptosis of AM．
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