Changes Of PTEN Expression In Pulmonary Artery Of Rats With Chronic Hypoxic Pulmonary Arterial Hypertension

Objective:The SD rats is exposed to different chronic normobaric hypoxic time in order to establish the chronic normobaric hypoxic rat model.To observe the changes of PTEN protein expression level in pulmonary arteries of rats induced by hypoxia, we preliminarily explore the effect of PTEN in the development of chronic hypoxic pulmonary hypertension.Methods:(1)Healthy adult male Sprague Dawley(SD) rats were exposed to normobaric hypoxia to induce PH model. The rats were randomly divided into six groups, and exposed to normoxia control and to normoxia hypoxia for 1, 3, 7, 14 and 21 d groups. Apart from the control group, other groups were exposed to normobaric hypoxia to induce HPH model.All SD rats in the experiment were given the same standard laboratory food and housed in a standard environment.(2)After the end of each hypoxic phase, right ventricle systolic pressure(RVSP)was measured via catheterization of pulmonary artery.The hearts of rats were excised,dissected and weighed to determine right ventricle hypertrophy index(RVHI) as the ratio of right ventricle(RV) to left ventricle(LV) plus septum(S).(3)Pulmonary arteries in the same site of rats were isolated and stained with hematoxylin and eosin(HE).Pathological changes of the pulmonary arteries were observed under optical microscope.(4)Different cell components of the rat pulmonary arteries were isolated andextracted.The changes of PTEN and p-PTEN protein in pulmonary arteries were also detected by Western blotting.Results:(1)RVSP increased significantly after hypoxic exposure for 1, 3, 7, 14 and 21 d when compared with the normoxia control(P<0.05); There were significant rise in RVHI after hypoxic exposure for 3, 7, 14 and 21 d(P<0.05).(2)The pathological changes of the pulmonary arteries were significant at 3,7,21 d.Pulmonary arteries smooth muscle has a trend of proliferation.Pulmonary arteries generally thickened and vascular cavity was constricted.(3)There were expressions of PTEN and p-PTEN in the control and hypoxic groups.(4)PTEN protein expression decreased after chronic hypoxia than normal control groups(P>0.05).There was a tendency of increase in p-PTEN after hypoxia exposure, and p-PTEN protein expression level significantly increased at 21 d after hypoxic exposure(P<0.05).Conclusions:(1)Chronic hypoxia contributes to vascular remodeling including medial hypertrophy,right ventricular hypertrophy and pulmonary hypertension of rats.(2)There were expressions of PTEN and p-PTEN in the normoxia control and hypoxic groups.(3)The decrease in protein expression of PTEN and increase of p-PTEN may play an important role in the development of the chronic hypoxia-induced pulmonary hypertension.