The Research About The Effects Of Tadalafil On Pulmonary Arterial Remodeling In Rats With Pulmonary Hypertension Induced By Monocrotaline

BackgroundPulmonary hypertension is the most common complication of the left-to-right shunt congenital heart disease,because of left-to-right shunt,pulmonary circulation continues to remain high perfusion,pulmonary artery wall continued over-exposed to the impact of blood flow,resulting in damage to the endothelial cells,smooth muscle hyperplasia,pulmonary vascular stenosis,pulmonary vascular remodeling resulting in increased pulmonary artery pressure,but for the treatment of congenital heart disease,pulmonary hypertension is a major prognostic factors mainly determine the level of pulmonary artery pressure and pulmonary vascular disease severity,left-to-right shunt blood to the pulmonary circulation was the sighificant increase and cause increased pulmonary vascular filling pressure, pulmonary vascular blood flow to speed,causing vascular reactivity contraction,and on this basis increased mechanical stress on the blood vessels,due to the persistence of the above factors lead to pulmonary vascular structural remodeling and pulmonary hypertension,and continue to study,the gene BMPR2mutation has a close relationship with pulmonary vascular remodeling.Tadalafil as a PDE5inhibitor,is increasingly used in the treatment of pulmonary hypertension now,but its mechanism of action and efficacy,and relative to the weight of the dose required to effectively inhibit pulmonary vascular remodeling has not been understanding fully.ObjectiveThe purpose of this research is to explore the way of establishment the rat model of pulmonary hypertension,and observe whether tadalafil can reduce pulmonary hypertension,and prevent or mitigate the pulmonary vascular remodeling,so lay the foundation for the clinical application.MethodsThe30healthy Wistar rats were divided into3groups randomly and every group have10rats.:group A is the model of pulmonary hypertension,were given a single subcutaneous injection of60mg/kg monocrotaline at the back, and then free feeding and drinking;group B were injected with some does monocrotaline as group A and kept feeding under the same conditions,and after4weeks with tadalafil0.5mg/kg-d by gavage4weeks;group C were injected with equivalent saline at the back and kept feeding under the same conditions of the group A and B.all of the three groups were feeding8weeks up to the end of the experiment.then were measuring their weight and the index of the right ventricular hypertrophy was calculated by RV/(LV+S);and pulmonary artery with HE staining,calculate the pulmonary artery wall thickness and lumen area,after that the tissue of pulmonary were obtained to measure BMPRⅡby RT-PCR,and evaluate tadalafil on pulmonary artery remodeling.ResultsGroup A of final body weight relative to the C group were lower (P<0.05), B, C, body weight was not statistically significant (P>0.05). Group A of relative expression of BMPR Ⅱ B, C group was significantly reduced。Group A of right ventricular hypertrophy and pulmonary vascular structural changes was significantly higher than B and C group (P<0.01), while group B relative to group A has been significantly reduced (P<0.05).Conclusion1、monocrotaline can establish rat model of pulmonary hypertension successfully, and induces the pulmonary arterial occur reconstructive change.2、BMPR2showed decreased in pulmonary hypertension inferred it play a key role in the occurrence and development of pulmonary hypertension,and to reduce the level of a certain degree reflects the severity of pulmonary hypertension.3、Tadalafil can inhibit the pulmonary arterial reconstruction in Wister rats with pulmonary hypertension,but the dose relevant weight need farther research.