Effect Of Propofol On Angiotensin Converting Enzyme 2 In Monocrotaline Induced Pulmonary Hypertension In Rats

Objective :To investigate the effect of propofol on monocrotaline induced pulmonary arterial hypertension(ACE2)in rats,and to investigate the mechanism of action.Method : Stochastic indicator method is used on average only 32 SD rats can be divided into four groups(n = 8): control group,MCT group,propofol group,propofol group + A779,after intraperitoneal injection of three groups of 60mg/kg MCT amount of saline injection(control group)after induction,two groups of daily for an injection of propofol respectively after 10 mu mol/L,propofol 10 mu mol/L and A779(concentration of 2 mg/ml),the former two groups of injection amount of normal saline;4 weeks after measuring the rat mean pulmonary artery pressure(m PAP),lung tissue HE staining analysis of film thickness index(WT)in pulmonary artery and pulmonary small artery obstruction degree;Western blot detection ACE2 in lung tissue,Mas,P-Akt,P-e NOS expression level;ELISA to detect lung tissues angiotensin 1-7(Ang-(1-7));Results : Blank control group,model group(MCT),propofol group,propofol +A779 rat m PAP were(11.37±2.17)mm Hg,(32.43±4.22)mm Hg,(15.82±2.12)mm Hg,(18.13±2.31)mm Hg,WT are respectively(15.63±11.12)%,(78.01±17.40)%,(22.64±12.95)%,(63.67±16.43)%.Compared with blank control group,propofol group,propofol + A779 rats m PAP slightly elevated(P=0.001,P=0.005),while the MCT group increased significantly(P<0.001);Pulmonary vascular blank control group,model group,no obvious narrowed lumen basic block,the basic normal lumen propofol group,propofol group + A779 lumen obvious hyperplasia;Compared with MCT group,blank control group,propofol group rats WT significantly reduced(P=0.003,P=0.002),compared with propofol group,propofol + A779 group rats WT significantly increased(P=0.002).ACE2 in propofol group and blank control group,Mas,P-Akt,P-e NOS increased significantly in the model group(propofol group compared with model group and blank control group,P<0.001).Propofol + A779 rat lung group Mas expression level and decreased obviously in the propofol group(P=0.005)The expression of Ang-(1-7)in lung tissues of rats in each group was detected by ELISA.The propofol group(75.31 + 6.51)pg/ml and the control group(81.75 + 5.80)pg/ml were significantly higher than those in the MCT group(34.55 + 5.72)pg/ml(P<0.001).Propofol group +A779(41.14 +8.03)pg/ml,compared with propofol group(75.31 + 6.51)pg/ml,decreased obviously(P<0.001).The content of NO in lung tissue of rats was detected by nitrate reductase method: Propofol group(6.17 + 0.90),mu mol/g and control group(6.70 + 0.84)mu mol/g,compared with group MCT(2.83 + 0.82)mu mol/g,increased significantly(P<0.001).Propofol group +A779(2.99 + 0.98)mol/g was lower than propofol group(6.17 + 0.90)mu mol/g(P<0.001).Conclusion: Propofol can adjust the ACE2 to suppress the development of pulmonary hypertension in pulmonary hypertension,the effect may be related to activation of ACE2-Ang-(1-7)-Mas shaft,which in turn activated Akt/e NOS downstream signaling pathways.