血管紧张素Ⅱ受体在大鼠机械通气所致肺损伤中的作用

The role of activation of angiotensin Ⅱ receptor in ventilator-induced lung injury in rats

【摘要】目的研究血管紧张素Ⅱ受体（AT1型）在机械通气所致肺损伤中的作用。方法40只健康SD大鼠随机分成4组（n=10）：对照组（A组）、正常潮气量机械通气组（B组）、大潮气量机械通气组（C组）和大潮气量机械通气加洛沙坦预处理组（D组）。A组不行机械通气，B组潮气量（VT）为10ml／kg，C组VT为40ml／kg，D组实验前1周每天用血管紧张素Ⅱ受体（AT1型）特异性阻滞剂洛沙坦溶液100mg灌胃后，行大潮气量机械通气，VT为40ml／kg。机械通气2h后处死大鼠，收集肺组织和支所管肺泡灌洗液，光镜下观察肺组织病理改变，RT-PCR法检测A组、B组和C组肺组织中AT。受体mRNA的表达，同时测定支气管肺泡灌洗液总蛋白、白细胞计数、肺湿，干重比（W／D）和中性粒细胞髓过氧化物酶（MPO）、巨噬细胞炎症蛋白-2（MIP-2）的水平。结果C组和D组肺泡间隔明显增厚，肺泡腔内有渗出物，可见较多的炎性细胞浸润，其病理损伤程度较A组和B组重。与A组和B组比较，C组和D组AT1受体mRNA表达、支气管肺泡灌洗液中总蛋白浓度、白细胞计数、MIP-2浓度和肺组织中MPO活性、W／D均增高（P〈0．01）；与C组比较，D组上述各项指标均降低（P〈0．05或0．01）。结论AT1受体参与了大鼠机械通气所致肺损伤。

Objective To study the role of activation of angiotensin Ⅱ receptor （AT1） in ventilatorinduced lung injury （VILI） in rats. Methods Forty healthy male SD rats weighing 300-350 g were randomly divided into 4 groups （n = 10 each） ： A control group received no mechanical ventilation; B normal VT group （VT = 10 ml/kg） ; C large VT group （VT = 40 ml/kg ） and D losartan ＋ large VT group （VT = 40 ml/kg）. All animals were anesthetized with intraperitoneal 20% urethane and tracheostomized. The animals in group B, C and D were mechanically ventilated with room air. VT was set at 10 ml/kg in group B or 40 ml/kg in group C and D. Respiratory rate was set at 80 bpm and I ： E at 1 ： 1. In group D losartan （specific AT, blocker） 100 mg in 2 ml of normal saline was injected through a gastric tube into stomach once a day for 7 consecutive days before mechanical ventilation. The animals were sacrificed by exsanguination at the end of 2 h mechanical ventilation. Their lungs were removed for （ 1 ） lung lavage and determination of total protein and macrophage inflammatory protein-2 （MIP-2） concentrations in broncho-alveolar lavage fluid （BALF）, （2） determination of myeloperoxidase （MPO） activity and AT. mRNA expression in lung tissue, （3） determination of W/D lung weight ratio and （4） microscopic examination. Results The inflammatory response as evidenced by thickening of alveolar septa, inflammatory cell infdtration and exudate in alveolar sacs was severer, the MPO activity and AT, mKNA expression in the lung tissue were significantly increased and the total protein and MIP-2 concentrations in BALF and W/D ratio were significantly higher in group C （large VT ） than in normal VT group （B）. Losartun pretreatment significantly attenuated the large VT ventilation-induced changes. Conclusion AT, receptor is involved in ventilator-induced lung injury in rats.