The Effect Of Acteoside From Cistanche On Rats With High Altitude Hypoxia Pulmonary Hypertension

Objective: To observe the effect of acteoside from C.tubulosa.on plateau hypoxia pulmonary hypertension rats and it's possible mechanism.Method: 1.Gave drugs for 1 week before kept rats in simulated 5000 m altitude plateau artificial hypobaric hypoxia chamber for 28 days.72 SD rats were divided into control group,model group,sildenafil group(6.25mg/kg)and acteoside high,medium and low dose group(50mg/kg?25mg/kg?12.5mg/kg),each group had 12 rats.Sildenasil,Acteoside were preventively administered for 35 days.2.Measure the mean pulmonary artery pressure,right ventricular systolic pressure,and the right ventricular hypertrophy index were calculated.3.Observed the pathological changes of rat lung and heart tissue.4.Detected the content of ET-1,VEGF,and NO,and detect NOS,iNOS,eNOS enzymatic activity in lung homogenate.5.Determined HIF-1? mRNA and protein expression.Result: 1.Compared with the control group,mean pulmonary artery pressure,right ventricular systolic pressure and right ventricular hypertrophy of model group rats were significantly increased(P ?0.01).Compared with the model group rats,acteoside high and middle dose group could reduce the mean pulmonary arterial pressure,right ventricular systolic pressure(P?0.05).2.Compared with the control group,around bronchia inflammatory cell infiltration were evident,the pulmonary arteriolar wall were markedly thickened and the lumen were narrowed,myocardial cell hypertrophy were visible.Compared with the model group rats acteoside low,medium and high dose groups and sildenafil group could inhibit rat pulmonary vascular thickening inflammatory cell infiltration and myocardial cell hypertrophy.3.Compared with the control group,ET-1,VEGF content were increased while NO content,enzyme activity of NOS and eNOS were decreased in rat lung homogenate(P ? 0.01)and iNOS were increased in rat lung homogenate(P ? 0.01).Compared with the model group rats,Acteoside medium and high dose groups and sildenafil group could reduce ET-1,VEGF content while increase NO content and enzyme activity of NOS,eNOS.decreased enzyme activity of iNOS(P?0.01)in lung homogenate.4.Compared with the control group,the expression of HIF-1? mRNA and protein expression increased in lung tissue(P?0.01).Compared with the model group rats,acteoside medium and high dose groups and sildenafil group could reduced the HIF-1? protein and mRNA expression in pulmonary tissue(P?0.01).Conclusion: 1.Keeping rats in simulated 5000 m altitude plateau artificial hypobaric hypoxia chamber for 30 days can successfully establish rat model of pulmonary hypertension.2.By enhance the NO pathway function,inhibition of vasoconstriction,expression of HIF-1? down regulation,inhibition of pulmonary vascular remodeling,reduce damage to endothelial function,acteoside probably could reduce the mean pulmonary artery pressure and right ventricular hypertrophy,improve pathological change of ventriculus dexter and lung in rats with pulmonary hypertension.