The Effect Of Endostar To Pulmonary Vascular Remodeling In Chronic Obstructive Pumonary Disease

Objective: To detect the changes of VEGF expression in the development of COPD. Find out the relationship between VEGF expression and the pulmonary vascular remodeling, also the relationship between VEGF expression and pulmonary hemodynamics. To understand the effect of endocardial blood vessel production inhibiting factor(Endostar) to VEGF expression in animal mode lung tissue of COPD. To research the changes of pulmonary vascular remodeling and pulmonary hemodynamics after use Endostar. Find out the effect of VEGF in the development of COPD and the influence of the Endostar to pulmonary vascular remodeling in COPD. Giving a new way to the treatment of COPD.Methods : There are two part of this research. Part 1: To detect the changes of VEGF expression in the development of COPD. Find out the relationship between VEGF expression and the pulmonary vascular remodeling, also the relationship between VEGF expression and pulmonary hemodynamics. The experiment uses the smog exposition with the low oxygen to make the animal mode of COPD.( There are four group in this part of the research, 8 SD rat in each group randomly): Healthy control group (group A): 0.2 ml saline water was installed intratracheally once at first and forteenth day for all rats, testing after 4 weeks.. Chronic bronchitis group (group B):200μg lipopolysaccharide (LPS) was installed intratracheally once at first and forteenth day for all rats, testing after 4 weeks. COPD group (group C): 200μg LPS was installed intratracheally once at first and forteenth day and the rats were exposed to cigarette smoke 1h/d for 4 weeks. low oxygen with COPD group (group D):200μg LPS was installed intratracheally once at first and forteenth day and the rats were exposed to cigarette smoke 1h/d for 6 weeks. In last 2 weeks chronic hypoxia (FiO2=0.18) 8h/d were performed simultaneously.Part 2: To understand the effect of endocardial blood vessel production inhibiting factor(Endostar) to VEGF expression in animal mode lung tissue of COPD. To research the changes of pulmonary vascular remodeling and pulmonary hemodynamics after use Endostar. ( There are four group in this part of the research, 8 SD rat in each group randomly): Endostar intervention group include: A1(Normal group),B1(Chronic bronchitis intervented group),C1(COPD intervented group), D1(low oxygen with COPD intervented group). Animal model were made the same as the corresponding group, Endostar 7.5mg.m2-1.d-1(1.25mg.Kg-1) were injected into the rats in each drug group from the third week. The saline water which was the same dose of Endostar was injected into the rats in A1 group from the third week.We examine the following target of rat in each group after animal model made completely: The airway resistance, pulmonary hemodynamics,include RVSP,mPAP and RVHI were determinated in each group. HE staining of lung tissue and VG+Victoria blue triple staining was used to observe the pulmonary vascular remodeling in pathological changes, includeing WT% and WA%. Immunohistochemistry was used to detecte VEGF expression in rat lung tissue of every group. ELISA was used to detect VEGF expression in lavage fluid (BALF) and serum in each group and RT-PCR were detected of VEGF mRNA in lung tissue expression. Western blot used to detect the VEGF protein expression. Analyzes the relevance between VEGF expression and the pulmonary vascular remodeling, also the relevance between VEGF expression and pulmonary hemodynamics.Results: 1.Airway resistance and the target of pulmonary hemodynamics (mPAP,RVSP,RVHI):Compare to group A,the airway resistance and the target of pulmonary hemodynamics of group B were no different to that of group A(P﹥0.05). But these above target of group C and D were higher than that of group A(P<0.05). After using Endostar,the airway resistance and the target of pulmonary hemodynamics of group B1 were no different to that of the corresponding group B(P﹥0.05). But these above target of group C1 and D1 were significantly decreased than that of the corresponding group C and D(P<0.05). The above target of group A1 which were used saline were no different to that of the corresponding group A(P﹥0.05).2. The target of pulmonary vascular remodeling(WT%,WA%):Compare to group A,the target of pulmonary vascular remodeling of group B were no different to that of group A(P﹥0.05). But these above target of group C and D were higher than that of group A(P<0.05). After using Endostar,the target of pulmonary vascular remodeling of group B1 were no different to that of the corresponding group B(P﹥0.05). But these above target of group C1 and D1 were significantly decreased than that of the corresponding group C and D(P<0.05). The above target of group A1 which were used saline were no different to that of the corresponding group A(P﹥0.05). 3. The expression of VEGF: Compare to group A,the VEGF mRNA and protein of group B were higher than that of group A(P<0.05);but the concentration of VEGF in BALF and serum,also the VEGF expression of pulmonary vascular were no different to that of group A(P﹥0.05). These above target include VEGF mRNA and protein expression,concentration of VEGF in BALF and the VEGF expression of pulmonary vascular of group C and D were all higher than that of group A(P<0.05). But the concentration of VEGF in serum of group C were no different to that of group A(P﹥0.05). After using Endostar,the VEGF mRNA and the concentration of VEGF in serum of group B1 were decreased than that of the group B;and the other target of group B1 were no different to that of the corresponding group B(P﹥0.05). These above target of group C1 and D1 were significantly decreased than that of the corresponding group C and D(P<0.05). The above target of group A1 which were used saline were no different to that of the corresponding group A(P﹥0.05).4. The releationship between the expression of VEGF and the target of pulmonary hemodynamics and pulmonary vascular remodeling: There was positive correlation between the expressions of VEGF and the target of pulmonary hemodynamics(mPAP,RVSP,RVHI)and pulmonary vascular remodeling(WT%,WA%). After using Endostar,the expression of VEGF were decreased and the target of pulmonary hemodynamics and pulmonary vascular remodeling were gradually improve at the same time.Conclusions:①In the the different stages of the development of COPD,the pulmonary vascular remodeling have appeared at the early stages of the development of COPD. With the development of the desease,the pulmonary vascular remodeling increase gradually,and pulmonary hemodynamics anomaly were appeared at the same time. The pulmonary vascular remodeling was closely releated to the severity of COPD.②VEGF participated in all process of the development of COPD ,the VEGF expression advances gradually with the aggravation of COPD. It wrer possibly promotes the COPD course progress through the pulmonary vascular remodeling.③Endostar can decrease the pulmonary vascular remodeling and abnormal of pulmonary hemodynamics through suppresses the production of endocardial VEGF and declines the expression of VEGF.