肺保护性机械通气对急性肺损伤家兔血氧合指数及支气管灌洗液细胞因子和酶的影响

Effect of pulmonary preventive mechanical ventilation on the blood oxygenation index and bronchoalveolar lavage fluid and enzyme in rabbits with acute lung injury

目的:观察不同机械通气模式对实验家兔血氧合指数和支气管肺泡灌洗液中肿瘤坏死因子α、白细胞介素1β、白细胞介素6、乳酸脱氢酶、碱性磷酸酶的影响,探讨保护性机械通气减轻机械通气相关肺损伤的生物学机制。方法:2003-05/2004-02在解放军总医院动物实验中心完成动物实验,细胞因子的测定在解放军总医院呼吸内科实验室完成。实验选用清洁级健康雄性家兔30只,随机分为5组,每组6只。①油酸对照组:油酸注射、仰卧位、呼气末正压0kPa、潮气量13～15mL/kg。②小潮气+呼气末正压组:油酸注射,仰卧位,呼气末正压0.78kPa,潮气量8mL/kg。③单纯俯卧位组:注射油酸,俯卧位,呼气末正压0kPa,潮气量13～15mL/kg。④俯卧位+小潮气+呼气末正压组:油酸注射、俯卧位、呼气末正压0.78kPa,潮气量8mL/kg。⑤空白对照组:不注射油酸,仰卧位,呼气末正压0kPa,潮气量13～15mL/kg。通过将家兔油酸型急性肺损伤模型应用4种不同模式机械通气,比较支气管肺泡灌洗液中肿瘤坏死因子α,白细胞介素1β,白细胞介素6和乳酸脱氢酶、碱性磷酸酶的变化。结果:最终进入结果分析家兔30只。①5个实验组家兔基础氧合指数无明显差异,置管对氧合指数无影响(P>0.05),4个注射油酸1.5h后的实验组家兔,氧合指数明显低于空白对照组。②油酸对照组和单纯俯卧位组家兔支气管肺泡灌注液肿瘤坏死因子α水平犤(15.523±6.884),(9.038±4.737)μg/L犦明显高于小潮气+呼气末正压+俯卧位组和空白对照组犤(0.985±0.538),(0.357±0.151)μg/L,P<0.05犦;油酸对照组肿瘤坏死因子α水平明显高于小潮气+呼气末正压组犤(0.982±0.357)μg/L,P<0.05犦。③单纯俯卧位组白细胞介素1β水平犤(2.208±0.828)μg/L犦明显高于小潮气+呼气末正压+俯卧位组和空白对照组犤(0.596±0.399),(0.472±0.200)μg/L,P<0.05犦。④油酸对照组和单纯俯卧位组家兔支气管肺泡灌注液白细胞介素6水平犤(1491.212±549.590),(1102.14±477.368)μg/L犦明显高于小潮气+呼气末正压+俯卧位组和空白对照组犤(177.803±53.914),(295.855±86.609)μg/L,P<0.05犦;油酸对照组白介素6水平明显高于小潮气+呼气末正压组犤(229.332±54.418)μg/L,P<0.05犦。⑤小潮气+呼气末正压组、小潮气+呼气末正压+俯卧位组、空白对照组家兔支气管肺泡灌注洗液碱性磷酸酶、乳酸脱氢酶活性明显低于油酸对照组犤碱性磷酸酶:(0.48±0.18),(0.44±0.15),(0.59±0.39),(1.19±0.37)μkat/L;乳酸脱氢酶:(0.07±0.05),(0.06±0.05),(0.05±0.01),(0.25±0.18)μkat/L,P<0.05犦。结论:肺保护性通气不仅可以改善氧合,同时可以抑制支气管肺泡灌洗液中肿瘤坏死因子α、白细胞介素1β、白细胞介素6和乳酸脱氢酶、碱性磷酸酶的释放,减轻血管内皮细胞损伤及降低通透性,减少渗出,减少呼吸机相关肺损伤。

AIM:To observe the effects of different mode of mechanical ventilation on the blood oxygenation index and tumor necrosis factor alpha,interleukin-1-beta,interleukin-6,lactate dehydrogenase and alkaline phosphatase in bronchial alveolar lavage fluid in experimental rabbits,and investigate the biological mechanism of protective mechanical ventilation in relieving ventilator induced lung injury. METHODS:The experiment was carried out in the animal test center of General Hospital of Chinese PLA between May 2003 and February 2004.Cytokine was examined in the respiratory department of General Hospital of Chinese PLA.Thirty healthy male rabbit of clean degree were randomly divided into five groups with 6 in each group:① oleic acid control group: the rats were injected with oleic acid,supine position,positive end expiratory pressure was 0 kPa,tidal volume was 13 to 15 mL/kg.② low tidal volume + positive end expiratory pressure group:rats were injected with oleic acid,supine position,positive end expiratory pressure was 0.78 kPa,tidal volume was 8 mL/kg.③ prone position group:rats were injected with oleic acid,prone position,positive end expiratory pressure was 0 kPa,todal volume was 13 to 15 mL/kg.④ low tidal volume+ prone position+ positive end expiratory pressure group:rats were injected with oleic acid,prone position,positive end expiratory pressure was 0.78 kPa,tidal volume was 8 mL/kg.⑤ blank control group:rats did not receive inject with oleic acid,supine position,positive end expiratory pressure was 0 kPa,tidal volume was 13 to 15 mL/kg.The changes of tumor necrosis factor alpha,interleukin 1 beta,interleukin 6,lactate dehydrogenase and alkaline phosphatase in bronchial alveolar lavage fluidacute in rabbit models of lung injury induced by oleic acid were compared by using 4 different kinds of mechanical ventilation. RESULTS:Thirty rabbits were involved in the analysis of results finally.① The oxygenation index was not obviously different among the 5 experimental groups, and it was not affected by operation(P >0.05);At 1.5 hours after injection of oleic acid,the oxygenation index was markedly lower in the 4 experimental groups than in the blank control group.② The tumor necrosis factor alpha levels in BALF of rabbits in the oleic acid control group and prone position group[(15.523± 6.884),(9.038± 4.737) μ g/L] were obviously higher than those in the low tidal volume+ positive end expiratory pressure + prone position group and blank control group[(0.985± 0.538),(0.357 ± 0.151) μ g/L](P< 0.05);It was also markedly higher in the oleic acid control group than in the low tidal volume+ positive end expiratory pressure group[(0.982± 0.357) μ g/L] (P< 0.05).③ The interleukin 1 beta level was obviously higher in the prone position group[(2.208± 0.828) μ g/L] than in the low tidal volume+ positive end expiratory pressure+ prone position group and blank control group[(0.596± 0.399),(0.472± 0.200) μ g/L] (P< 0.05).④ The interleukin 6 levels in the oleic acid control group and prone position group[(1 491.212± 549.590),(1 102.14± 477.368) μ g/L] were remarkably higher than those in the low tidal volume+ PEEP+ prone position group and blank control group[(177.803± 53.914),(295.855 ± 86.609)μ g/L] (P< 0.05);It was obviously higher in the oleic acid control group than in the low tidal volume group+ positive end expiratory pressure group[(229.332± 54.418)μ g/L](P< 0.05).⑤ The rabbits in the low tidal volume group+ positive end expiratory pressure group, tidal volume group+ positive end expiratory pressure+ prone position group and blank control group had obviously lower levels of alkaline phosphatase[(0.48± 0.18),(0.44± 0.15),(0.59± 0.39) μ kat/L] and lactate dehydrogenase[(0.07± 0.05),(0.06± 0.05),(0.05± 0.01) μ kat/L] than in the oleic acid control group[(1.19± 0.37), (0.25± 0.18) μ kat/L](P< 0.05). CONCLUSION:Lung protective mechanical ventilation can not only improve oxygenation,but also inhibit the releases of tumor necrosis factor alpha,interleukin 1 beta,interleukin 6,lactate dehydrogenase an