Changes Of ERK1/2、p38MAPK In Pulmonary Vascular Remodeling Of Chronic Hypoxia-Induced Rat Pulmonary Hypertension

Background Pulmonary vascular remodeling is the pathological basis of common respiratory system disease, such as chronic obstructive pulmonary disease (COPD), pulmonary hypertension, etc. In recent years, role of pulmonary vascular after hypoxic exposure cause people’s attention. There are evidences show that ERK1/2、 p38MAPK expresse widely,such as cancerous tissue, kidney tissue and lung tissue, and they participate many kinds of physiological and pathological process,such as inflammatory reaction, cell stress, cell apoptosis, cell proliferation and so on. however,studies about the expression of ERK1/2、p38MAPK in pulmonary vascular have been few repoted.Objective In this study, with hypoxia-induced pulmonary hypertension rats model, to investigate the expression variation of ERK1/2、p38MAPK in rat pulmonary arteries and its role in pulmonary vascular remodeling.Methods Establish the rat model of pulmonary hypertension with sixty male SD rats which were randomly divided into a normal control group, hypoxic exposure1day,3days,7days,14days and21days groups and with10rats in each group. Right ventricular systolic blood pressure (RVSP) and right ventricular hypertrophy index (RV/(LV+S)) were determined.Observe the morphology change of rat lung tissue with hematoxylin-eosin (HE).RVSP, RV/(LV+S) and results of HE as indexs of model.The expression of ERK1/2、p38MAPK protein in rat pulmonary arteries of each group was detected by immunohistochemistry.Results (1) With the extension of hypoxic exposure, compared with controls. RVSP increased obviously (with0day, p<0.05,23.76±0.82mmHg, n=8), and reach the top at7days.(2) With the extension of hypoxic exposure, compared with controls, RV/(LV+S) increased significantly (with0day, p<0.05,100%, n=8).(3) The results of hematoxylin-eosin (HE) staining showed that pulmonary artery have obvious pathological changes after hypoxic exposure at7,14and21days, the pulmonary artery walls of distal and proximal regions from pulmonary hypertension rats thickened obviously.(4) The results of immunohistochemical staining showed that ERK1/2、p38MAPK protein were widely distributed in pulmonary arterial endothelial cells, smooth muscle cells and]fibroblasts. And the longer of the time of hypoxic exposure, the more of protein expression.Conclusion ERK1/2、p38MAPK protein expression in rat pulmonary vascular might increase after hypoxic exposure and participate in pulmonary vascular remodeling.