Effects And Mechanisms Of Angiotensin Converting Enzyme 2 And Angiotensin 1-7 In Lipopolysaccharide -induced Rat Acute Lung Injury

ObjectiveTo observe the effects of ACE2 and Ang 1-7 on cultured rat PMVEC stimulated by AngⅡand lung tissue in LPS-induced ALI, and to investigate the possible mechanism of ACE 2 on PMVEC and lung tissue in rat ALI induced by LPS. Meanwhile, to study the role of Ang 1-7 in the protective mechanism of ACE2 in LPS-induced rat ALI.MethodsIn vitro, rat PMVEC were isolated and cultured and incubated with LPS ( 10μg / ml ) or AngⅡ( 10-7 mmol / L ) for 90 min; PMVEC monolayer were pre-exposured to ACE2 inhibitor ( 10-7 mmol / L ) and Ang 1-7 receptor agonist ( 10-6 mmol / L ) for 30 min respectively, after then, the cells were incubated with AngⅡ( 10-7 mmol / L ) for 90 min. Microfiltrator was used to measure the changes of PMVEC monolayer permeability coefficient.In vivo,Wistar rats were intravenous administration of LPS ( 5 mg / kg ) for 30 min, after then treated with①ACE2 inhibitor ( 10 mg / kg ),②ACE2 inhibitor (10 mg / kg ) + Ang 1-7 receptor antagonist ( 10μg / kg ), and③Ang 1-7 receptor agonist ( 1 mg / kg ) for 5.5 h respectively. Lung wet / dry weight ratio was measured, and the pathologic changes of lung tissue were observed microscopically. Results1. Rat PMEVC was isolated and cultured in vitro successfully.2. Both LPS and AngⅡincreased the permeability of PMVEC monolayer significantly.3. In vitro, ACE2 inhibitor could enhance the AngⅡinduced PMVEC monolayer Kf increase, on the contrary, Ang 1-7 receptor agonist inhibited it.4. The model of acute lung injury was made by LPS injection.5. Both ACE2 inhibitor and/or Ang 1-7 receptor antagonist could enhance the increased wet / dry weight ratio of lung tissue induced by LPS and exacerbate the pathologic changes.6. Ang 1-7 receptor agonist inhibited the lung edema and improved the pathologic changes of LPS-induced ALI significantly.Conclusions1. Both LPS and AngⅡcould induced lung endothelial permeability increase significantly in cultured PMVEC.2. The lung wet/dry weight ratio increased markedly by LPS challenge. The lung tissue showed the pathologic changes of ALI induced by LPS in rat.3. Ang 1-7 relieved ALI in LPS-induced rat.4. ACE2 showed a protective effect on LPS-induced ALI through probably the positive regulation of Ang 1-7 levels.