| Background:Pulmonary arterial hypertension is a malignant pulmonary wascular disease caused by a variety of reasons, which is characterized by pulmonary arterial pressure and pulmonary vascular resistance are increased. Its main clinical symptoms:shortness of breath, chest pain, dizziness or syncope, hemoptysis. Formation mechanism of pulmonary irterial hypertension is not yet fully understood, but it has been confirmed: influence the balance between proliferation and apoptosis of pulmonary artery smooth muscle cells, eventually leading to the pulmonary artery reconstruction, which is an important feature of pulmonary hypertension. Increasing proliferation of smooth muscle cells and reducing apoptosis, which cause pulmonary artery medial thickening, lumen of blood vessel narrowing, pulmonary vascular resistance increased, resulting in increasing pulmonary artery pressure. The pathway of maintaining the vascular structures and the functional completeness accommodate unusually, and which lead up vascular remodeling. Studies have shown that pulmonary arteriospasm, intimal hyperplasia, remodeling or occlusion, and reduce the number of small arteries plays a very important role in the occurrence of pulmonary hypertension, the development process. So far, the iisease treatment is poor and the mortality rate is relatively high.Currently, this disease relies mainly on drug. Although these drugs can improve the quality of life of patients and prolong survival time of patients, these drugs are expensive, and the patient is easily to get drug resistance, and the side effects is obvious. We should give full play to the advantages of integrated traditional Chinese and Western medicine, and it has very important significance to study traditional Chinese medicinen for the prevention and treatment of pulmonary arterial hypertension. Shenfu yixin granule was based on the traditional Chinese medicine expert in our hospital and was developed out. It can significantly improve cardiac function, and it also can increase the cardiomuscula tension and renal blood flow, diuretic, and protect the cardiovascular. We do not know this granule if it can reduce pulmonary arterial pressure and pulmonary vascular resistance, can improve right heart failure,especially the function of promoting angiogenesis cannot be known. In this study, the shenfu yixin granule is used for the rats with pulmonary arterial hypertension, then we can observe and study further, and we investigate the mechanism of pulmonary hypertension and provide some new ideas and methods for the treatment of pulmonary arterial hypertension.Objective:Through investigating these rats, we can define that shenfu yixin granule have the effect on these rats with pulmonary hypertension induced by monocrotaline. This medicine can reduce the mPAP, RVSP, RVDP and PVR, and increase the CO and CI. It also can improve the right heart (?)ilure, and influence the pulmonary vascular endothelial function.Methods:According to prescription required, we chose the Chinese cut ;rude drug and made the shenfu yixin granule. The 40 SPF Wistar rats were randomly divided into four groups (n=10), the blank group, the model group,the western medicine group and the shenfu yixin granule group. The prepared MCT (60mg/Kg) were given subcutaneous in single dose to the model group, western medicine group and shenfu yixin granule group, then we could get the pulmonary arterial hypertension rats, at the same time, the plank group was given subcutaneous injection in single dose with normal saline (20mg/Kg). After 4 weeks, the blank groupthe and model group were given by gavage once a day for 4 weeks with normal saline, the western medicine group were given the sildenafil using the same method, the shenfu yixin granule were given the shenfuyixin granule using the same method. After 4 weeks, we observed the general conditions and activities every group, and got the hemodynamics including RVSP、RVDP、 mPAP、PVR using the pressure transducer and improved PE-50 catheters. we also got the CO、CI by the method of thermodilution. After the rats died, we could measure the right ventricular hypertrophy index, then we made the pathological section and observed the morphological changes in the ulmonary artery, and measured and calculated the wall hickness (WT%). Using the radioimmunoassay we could get the ;ndothelin-1, and using the immunohistochemistry we could observe he ETA-R in the Pulmonary vascular smooth muscle cells. Finally, we tested the biochemical index concerning the PAH’ prognosis.Results:1. The general conditions and activities with MCT After being given subcutaneous in single dose with MCT, the blank group, every rat always lived normally,hair soft and shiny, smooth breathing, eating normal. But other groups, the rats began to reduced activity and food after 1 week. Bristling hair, gray and dull with the rats, they bagan to appear the respiratory rapidity and lose the weight obviously after 1 week.After four weeks, the rats had significant losing weight, and oral lip and paw were cyanotic, some rats had the severe right heart failure and even died. After the drug intervention, the western medicine group and the shenfu yixin granule group had the better conditions than the model group, such as improving the mental state of rats, hair, breathing,activity, diet, weight.2. The results of hemodynamics The results of hemodynamics showed that the model group, the western medicine group and the shenfu yixin granule group had the higher mPAP、RVSP、RVDP and PVR. But the model group was higher than the western medicine group and the shenfu yixin granule group. The model group, the western medicine group and the shenfu yixin granule group had the lower CO and CI. But the model group was lower than the western medicine group and the shenfu yixin granule group. The western medicine group was a little lower than the shenfu yixin granule group.3. The observation of heart and lung Cutting the chest, we could find that the lungs were normal in the blank group, and the lungs had the elasticity and were pink. In the model group, the hearts were dark red, and right ventricles were thickening. The lungs were dark red or brown, swelling, a Little hard, we could find the petechial hemorrhage on the lungs. The western medicine group and the shenfu yixin granule group were better than the model group, they had a little differences.4. Right ventricular hypertrophy index In the model group, the western medicine group and the shenfu yixin granule group, the right ventricular hypertrophy index were higher than the blank group. The western medicine group and the shenfu yixin granule group were lower than the model group, but the western medicine group and the shenfu yixin granule group had a little difference.5. Observation of the pathological morphology Observing the histopathology after HE staining, in the model group, the western medicine group and the shenfu yixin granule group, we could observe the pulmonary small arterial wall, the smooth muscle proliferation, the intimal hyperplasia, the inflammatory cell infiltration, and the luminal stenosis, the pulmanary small arterial muscularization, the pulmonary vascular injury, the endothelial cell degeneration and swelling were obvious, even some cells began to mortify.This changes, the western nedicine group and the shenfu yixin granule group were better than the model group, and the western medicine group and the shenfu yixin granule group had a little difference. Measuring and calculating the ratio of the wall thickness and the blood vessel outer diameter, the model group, the western medicine group and the shenfu yixin granule group were higher han the blank group, but the western medicine group and the shenfu yixin granule group were lower than the model group, the western medicine group was lower than the shenfu yixin granule group.6. The endothelin-1 and the ETA-R In the model group, the western medicine group and the shenfu yixin granule group, the concentrations of the endothelin-1 were higher than the blank group. The western medicine group and the shenfu yixin granule group were higher than the model group, and the shenfu yixin granule group was higher than the western medicine group. That shows that the sildenafil and shenfu yixin granule can increase the concentrations of the endothelin-1, the sildenafil is obvious. The concentrations of the ETA-R, the model group, the western medicine group and the shenfu yixin granule group were higher than the blank group, especially, the western medicine group and the shenfu yixin granule group were lower than the model group. There was a little different between the western medicine group and the shenfu yixin granule group. That shows that the sildenafil and shenfu yixin granule can reduce the concentrations of the ETA-R in the pulmonary small vascular wall.7. The prognostic indicators concerning with pulmonary arterial hypertension The concentrations of the BNP, TnTI, UA, TBil were higher in the model group, the western medicine group and the shenfu yixin granule group than the blank group. The western medicine group and the shenfu yixin granule group were higher than the model group. There was a little different between the western medicine group and the shenfu yixin granule group.Conclusions:After the rats given the MCT subcutaneous in single dose, the model of pulmonary arterial hypertension was prepared. The pulmonary vascular remodeling and right ventricular hypertrophy was obvious, and the concentrations of endothelin and mPAP increased.Shenfu yixin granule and sildenafil have some protective effect on the pulmonary arterial hypertension rats induced by MCT. They can significantly improve the living condition of rats, and improve survival. After this experimental study,shenfu yixin granule can reduce the RVSP, RVDP, mPAP, PVR, and increase the CO and CI, this drug can reduce right ventricular hypertrophy index and the WT%, and reduce the ETA-R and the prognostic indicators. Overall, the shenfu yixin granule can improve the status of pulmonary hemodynamics, can prevent pulmonary vascular remodeling and endothelial function, can improve the function of right ventricular. The possible mechanism has to do with the function, maybe through reducing the expression of the ETA-R, then this function influence on the combination between the endothelin-1 and the ETA-R, influence on the pulmonary vascular remodeling and shrinking. |
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