驱动压肺保护性通气策略对慢性阻塞性肺疾病大鼠呼吸功能和血液动力学的影响

The effect of protective ventilation strategy driven by lung pressure on respiratory function and hemodynamics in rats with chronic obstructive pulmonary disease

目的探究驱动压肺保护性通气策略对慢性阻塞性肺疾病大鼠呼吸功能和血液动力学的影响。方法将雄性SD大鼠40只随机数字法分为空白对照组(Sham组)、COPD组、传统肺保护组、驱动压肺保护组,接动物呼吸机;分别于干预前(T_(0))、干预后即刻(T_(1))、干预后24 h(T_(2))3个时间段检测各组大鼠动脉血气指标(HR、pH、MAP、PaCO_(2)、PaO_(2))差异性;比较T_(2)时刻大鼠呼吸参数(吸气时间、呼气时间、呼吸幅度、呼吸频率)差异性;4周后检测大鼠呼吸功能[每分钟呼气量(VE)、最大呼气流量(PEP)、0.3 s用力呼气容积(FEV0.3)]后处死大鼠,取其肺部组织,确定各组大鼠肺组织炎性因子(IL-8、TNF-α、IL-18)、肺部组织病理形态、Smith评分及肺水肿程度比较。Western blot检测大鼠肺部组织内炎症小体NLRP3信号通路相关蛋白NLRP3、ASC、Caspase-1蛋白表达。结果与Sham组相比,T_(1)、T_(2)时刻COPD组HR、MAP、PaCO_(2)水平提升,PaO_(2)水平降低(P<0.05);与COPD组相比,肺保护组大鼠在T_(1)、T_(2)时刻HR、MAP、PaCO_(2)水平降低,PaO_(2)水平升高(P<0.05);驱动压肺保护组HR、MAP、PaCO_(2)水平低于传统肺保护组,PaO_(2)水平高于传统肺保护组(P<0.05);与Sham组相比,COPD模型的建立可以明显降低大鼠吸气时间、呼吸幅度、呼吸功能参数VE、PEP以及FEV0.3,提升呼气时间、呼吸频率、W/D值、炎性因子(IL-8、TNF-α、IL-18)、肺部组织肺泡、间质炎症以及出血程度及Smith评分(P<0.05);与COPD组相比,肺保护策略的实施可以明显提升大鼠吸气时间、呼吸幅度、呼吸功能参数VE、PEP以及FEV0.3,降低呼气时间、呼吸频率、W/D值、炎性因子(IL-8、TNF-α、IL-18)、肺部组织肺泡、间质炎症以及出血程度及Smith评分(P<0.05);其中驱动压肺保护性通气策略组大鼠改善效果较传统组更优(P<0.05);COPD模型的建立使得大鼠肺部组织内炎症小体NLRP3信号通路相关蛋白NLRP3、ASC、Caspase-1蛋白表达明显上调(P<0.05);与COPD组相比,肺保护策略的实施可以明显降低大鼠肺部组织内NLRP3、ASC、Caspase-1蛋白表达(P<0.05);其中驱动压肺保护性通气策略组大鼠肺部组织内NLRP3、ASC、Caspase-1蛋白表达低于传统肺保护通气策略(P<0.05)。结论驱动压肺保护性通气策略可以明显改善COPD大鼠肺部病理形态,提高呼吸功能,提高对大鼠血液动力学的稳定性,抑制炎症反应,其分子调控机制可能与抑制NLRP3炎症小体信号通路活性有关。

Objective The function and hemodynamics of the protective ventilation strategy of driving lung pressure on respiratory function in rats with chronic obstructive pulmonary disease(COPD)were explored in this study.Methods Forty male SD rats were selected as the research subjects.According to the experimental requirements,SD rats were divided into a blank control group(Sham group),a COPD group,a traditional lung protection group,and a driven compression lung protection group,and were subjected to animal ventilation.The differences in arterial blood gas indicators(HR,pH,MAP,PaCO_(2),PaO_(2))of rats in each group at three time periods before intervention(T_(0)),immediately after intervention(T_(1)),and 24 hours after intervention(T_(2))were compared.The differences in respiratory parameters(inhalation time,exhalation time,respiratory amplitude,respiratory frequency)of rats at T_(2) time were compared.After 4 weeks,the respiratory function(VE,PEP,FEV0.3)of the rats was tested,and the rats were euthanized.Lung tissue was taken to determine the inflammatory factors(IL-8,TNF-α,IL-18)in the lung tissue of each group of rats),pathological morphology of lung tissue,Smith score and degree of Pulmonary edema.Western blot was used to detect the expression of NLRP3 signaling pathway related proteins NLRP3,ASC,and Caspase-1 in inflammatory bodies of rat lung tissue.Results The levels of HR,pH,MAP,PaCO_(2),and PaO_(2) indicators in the Sham group remained stable during the T_(1) to T_(2) time period(P>0.05).Compared with the Sham group,the levels of HR,MAP,and PaCO_(2) in the COPD group were increased at T_(1) and T_(2),while the level of PaO_(2) was decreased(P<0.05).Compared with the COPD group,the lung protection group showed a decrease in HR,MAP,and PaCO_(2) levels at T_(1) and T_(2),while an increase in PaO_(2) levels(P<0.05).The levels of HR,MAP,and PaCO_(2) in the driving pressure lung protection group were lower than those in the traditional lung protection group,while the level of PaO_(2) was higher than those in the traditional lung protection group(P<0.05).Compared with the Sham group,the establishment of a COPD model significantly reduced the inspiratory time,respiratory amplitude,respiratory function parameters such as minute expiratory volume(VE),maximum expiratory flow(PEP),and forced expiratory volume(FEV0.3)in rats,and increased expiratory time,respiratory frequency,W/D value,and inflammatory factors(IL-8,TNF-α,IL-18),pulmonary tissue,alveolar and interstitial inflammation,degree of bleeding,and Smith score(P<0.05).Compared with the COPD group,the implementation of lung protection strategies significantly improved the inspiratory time,respiratory amplitude,respiratory function parameters such as minute expiratory volume(VE),maximum expiratory flow(PEP),and forced expiratory volume(FEV0.3)in rats,while reducing expiratory time,respiratory frequency,W/D value,and inflammatory factors(IL-8,TNF-α,IL-18),pulmonary tissue,alveolar and interstitial inflammation,degree of bleeding,and Smith score(P<0.05).The improvement effect of the driving pressure lung protective ventilation strategy group in rats was better than that of the traditional group(P<0.05).The establishment of a COPD model significantly upregulated the expression of NLRP3 signaling pathway related proteins NLRP3,ASC,and Caspase-1 in rat lung tissue(P<0.05).Compared with the COPD group,the implementation of lung protection strategy significantly reduced the expression of NLRP3,ASC,and Caspase-1 proteins in rat lung tissue(P<0.05).The expression of NLRP3,ASC,and Caspase-1 proteins in the lung tissue of rats in the protective ventilation strategy group was lower than that in the traditional lung protective ventilation strategy group(P<0.05).Conclusion The drive pressure lung protective ventilation strategy can significantly improve the pathological morphology of the lungs of COPD rats,improve the respiratory function and the stability of hemodynamics in rats,and inhibit inflammatory response.Its molecular regulation mechanism may be related to the inhibition of NLRP3 inflammatory complex signaling,which is worth further study.