内皮素-1在呼吸机所致肺损伤犬肺中的表达变化研究

Endothelin-1 expression in lung of ventilator-induced lung injury canine model

目的检测内皮素-1（ET—1）在呼吸机所致肺损伤（VIL1）模型肺组织的表达分布及变化。方法普通级犬随机分为正常对照组（N组n=6）、急性肺损伤（ALI）组（n=14）。用油酸静脉内注射制备ALI模型，制备成功后随机取2只作为ALI组，其他随机分为小潮气量机械通气组（LV组，n=6）、大潮气量机械通气组（即VII，I组，n=6），行不同潮气量机械通气6h（LV组潮气量6ml／kg，VILI组潮气量20ml／kg，呼气末正压=10cm H2O）。用HE染色病理观察各组病理变化并用Smith评分法进行肺损伤评分，用免疫组织化学法观察各组犬肺组织ET-1的分布，并比较各组ET-1变化。结果LV组及VIL1组出现肺泡隔增宽、炎性细胞浸润、肺泡出血、渗出和坏死等肺组织病理学改变，肺组织病理损伤评分LV组显著低于VIL1组（P〈0．01）。免疫组织化学结果显示：N组血管内皮细胞、肺泡有少量ET-1表达；LV组和VIL1组血管内皮细胞、肺泡ET-1的表达较N组显著增高（P值均〈0．01），且VIL1组血管内皮细胞及肺组织ET—1表达较LV组显著增高（P〈0．01）。结论在VIL1模型肺部血管上皮细胞及肺组织均存在ET1的异常高表达，提示ET-1可能参与VIL1的病理生理过程。

Objective To determine the change of endothelin 1 （ET-1） expression in the lung tissue of ventilator-induced lung injury （VILI） model. Methods The dogs were randomly divided into control group （N group, n =6） and acute lung injury （ALI） group （n =14）. ALI model was established by intravenously injecting with oleic acid. Thereafter two animals were obtained as ALI group, and the others were randomly divided into low tidal ventilation group （LV group, n=6） and high tidal ventilation group （i. e. VILI group, n=6）. The tidal volume was respectively 6 ml/kg and 20 ml/kg in LV group and VILI group, and positive end expiratory pressure was 10 cm H2O. Lung tissues were stained with HE, the pathological changes of lung injury were evaluated with Smith scoring, the distribution of ET-1 was observed with immunohistochemistry technique,and changes of pathology and ET-1 expression in different groups were compared. Results There were widened alveolar septum, inflammatory cell infiltration, alveolar hemorrhage, exudation, and necrosis in LV group and VILI group. The lung injury score in LV group was lower than that in VILI group （ P 〈0.01 ）. The immunohistoehemistry results showed that small amount of ET -1 was expressed in puhnonary vascular endothelial cells and alveoli of N group,et-1 expression in pulmonary vascular endothelial ceils and alveoli of LV group and VILI group was significantly higher than that in N group （all P 〈 0.01）, and ET-1 expression in VILI group was significantly higher than that in LV group （ P 〈0.01 ）. Conclusions ET-1 is overexpressed in pulmonary vascular endothelial cells and lung tissues of VILI model, which indicates that ET 1 may be involved in the pathophysiologic process of VILI.