| ObjectiveTo observe vascular remodeling and angiogenesis levels of interleukin-8(IL-8) as well as the relationship between vascular remodeling and angiogenesis and IL-8in pulmonary arterial hypertension rats.Methods1.48healthy male Wistar rats were randomly divided into two gruops:control group (n=8) and model group (n=40). And the40rats of model group were equally&randomly divided into four groups:7th day group,14th day group,21th day group,28th day group,10rats for each group. The model group rats were intraperitoneal injected MCT50mg/Kg while the rats in control group were intraperitoneal injected an equal volume saline.2. The model group rats were drawn from day7,4,21,28respectively. Control group was drawn from day28. All of the forty-eight rats were measured right ventricular systolic pressure (RVSP) and calculated right ventricular hypertrophy index (RVHI) after the rats were anesthetized measured right ventricular pressure through the right carotid vein when thoracotomy was accomplished. Completed measurement and then removed of the heart after ventricular blood was drawed then separated right ventricular free wall, interventricular septum and left ventricular. The weight ratio of right ventricular free wall vs interventricular septum plus left ventricular [RVHI=RV/ (L+S)] was to predict the extent of right ventricular hypertrophy.3. With Hematoxylin-Eosin staining of rat lung to observe morphology and arterial changes in the structure, and calculate the vessel wall area%(WA%):measured the total area (TA) of the vessel wall and vessel lumen area (VA).The ratio vessel wall area [WA%=(TA-VA)/TA] reflected the degree of remodeling of small pulmonary arteries hyperplasia.4. The angiogenesis was investigated by CD105immunohistochemistry of rat lung tissue to calculate the area ratio of the micro vascular density (MVD).5. The serum IL-8level was investigated by ELISA.6. Using SPSS13.0for windows to achieve all statistical analysis, with a significance level of0.05. All enumeration datas were showed as mean±SD. The differences between each group were analysed with one-way ANOVA test. Comparisons of parametric data between groups were indicated by Student-Newman-Keuls test. Mutual relations used linear correlation analysis to show.Results1. Lung tissue specimens observation:lung tissue of control group:the color was white with pink, the tissue was smooth and integrity. Model group rats lung tissue as time extended changed from grey to yellow white color, some parts were shrink, deformation.2. RVSP and RVHI:The right ventricular systolic pressure of model group rat’s appeared to rise from the7th day by comparison with the control group and increased significantly from the14th day. The right ventricle systolic pressure showed a continuous upward trend with time passed by. Similarly, right ventricular hypertrophy index also showed the same trend.3. Pulmonary artery morphology:Control group rat pulmonary artery endothelial cells were necrosis, blood vessel walls were smooth and continuity. Alveolar no swelling deformation, inerratic alveolar cavity without exudate。While the model group rat pulmonary artery endothelial cells as time progressed gradually were swelling and shedding; vascular stenosis deformation, marked hyperplasia of the membrane and was progressively increased the thickness trend, and some may had severe fibrosis. Inflammatory cell infiltration can be observed around the tube wall. Image analysis showed that the model group rats with pulmonary artery WA%showed increased trend along with the aggravation.4. Changes in serum levels of IL-8and lung tissue MVD:Compared with the control group, serum IL-8concentration and MVD of model group with the progress of the disease showed an upward trend (7days P<0.05,14days to28days P<0.01) and were higher than that of the control group at every time point (P<0.01).5. Linear corralation analysis showed that IL-8and WA%, MVD, WA%and MVD showed a positive correlation (r=0.644, r=0.641, r=0.721; P<0.01).Conclusion1. Model rats after MCT injection, along with the progression of RVSP&RVHI showed a rising trend. Significantly increased in the14th day, right ventricular pressure and right ventricular hypertrophy index were significantly heavier at the21th day with the PAH became more serious. With the progression pulmonary reconstructed, the model of MCT-induced pulmonary arterial hypertension in rats was successfully constructed.2. Model of lung tissue MVD with the progress of pulmonary arterial hypertension showed increased gradually, active prompt gradually with the progress of pulmonary arterial hypertension angiogenesis. Correlation analysis showed that serum IL-8and lung tissue MVD active angiogenesis in lung tissue and serum IL-8is closely linked.3. Model rats serum IL-8concentration and pulmonary WA%correlation analysis suggested that pulmonary arterial hypertension vascular remodeling and IL-8have a close relationship.Pulmonary WA%of lung tissue MVD correlation analysis showed that between pulmonary arterial hypertension in rats vascular remodeling and angiogenesis is not isolated, but closely linked.4. Pulmonary arterial hypertension is not only the emergence of vascular remodeling, also accompanied by the emergence and development of angiogenesis. IL-8,a proinflammatory factor and promote angiogenesis factor, not only reconstructed and pulmonary artery are closely linked, and played a certain role in pulmonary arterial hypertension angiogenesis.. |
PDF Full Text Request