Study On The Impact Of NF-κB In Pulmonaryarterial Endothelial Cell Of Vascular Remolding Induced By High Blood Flow On ADM And PGI2

BACKGROUND:Congenital pediatric cardiovascular system diseases hold a high proportion of pediatric disease, especially congenital heart disease. In China, the rate of children with congenital heart disease is about0.7%, which means that there are15-20millions of Children with heartdisease born each year. The pulmonary arterial hypertension (PAH), which can Occur at any stage of congenital heart disease, is a kind of syndrome with a high mortality and disability. And the treatment of pulmonary arterial hypertension draws significant attention at home and abroad. With an increase in pulmonary blood flow, the pulmonary shear stress (shear stress,SS) increased, and the pulmonary artery endothelial structure and function change, with the vascular smooth muscle cells proliferating and pulmonary vessels remodeling. The remodeling of pulmonary vessels is the pathophysiological basis of the formation of pulmonary hypertension.In1986, for the first time, the nucleoprotein, named NF-κB, which can specific bind of the enhancer kappa B sequence (GGG ACT TTC) in immunoglobulin kappa light chain gene, was detect in the nuclear extracts of B cells.Then people found its widely existence in vascular endothelial cells (VEC),vascular smooth muscle cells(VSMC)and myocardial cells. Many studies have confirmed that the pulmonary vasoconstriction and remodeling caused by high pulmonary blood flow has something to do with the enhancement of NF-κB activity. The pulmonary vasoconstriction and remodeling is inseparable with vasoactive substances, such as Endothelin1(ET1), angiotensin (AngⅡ), vascular endothelial growth factor(VEGF),platelet derived growth factor (PDGF), prostacyclin (PGI2), atrial natriuretic peptide (ANP), adrenomedullin (ADM) and nitric oxide (NO).Objective:We try to investigate how the activity of NF-κB to binding with Specific gene recognition sequence in pulmonary arterial endothelial cell influence the express of vasoactive substances in pulmonary endothelial cell, such as PGI2and ADM in high blood flow induced remodeling of pulmonary vascular,And establish the nucleoprotein factor kB (nf-kappa B) from left to right shunt in the rat model of vascular active substances of ADM and the relationship and application of PGI blocker pyrrolidine disulfide formate (PDTC) after the intervention.Research Method:The50male Wistar rats of4weeks old were randomly divided into four groups,Among them, There were15rats in the group of shunt operation (Tn group),15rats in the group of shunt operation and PTDC blocking (Ti group),10rats in sham-operated group(Co) and10in the control group(Cn group). Application of chloral hydrate anesthesia in rats, the Tn and Ti group rats by the method of casing connection, set up the left common carotid artery-external carotid venous shunt, Ti group of rats1hour before the surgery, according to120mg/kg. one hour before the operation for2weeks and the rats of Co group were processed in the same fashion as experimental group except undergoing surgery.Measurement the right ventricular systolic pressure(RVSP) through the cardiac catheterization, isolate the pulmonary artery endothelial cells in rats, and determinate the expression changes of vasoactive substances expressed in pulmonary arterial endothelial cell, such as adrenomeullin(ADM) and prostacyclin (PGI2) by immunohistochemical method. Research Results:After2weeks operatively, measuring the pulmonary artery pressure group, Calculates Qp/Qs average was2.32±0.44, The results indicate surgical shunt patency,Animal model is successfully established.Tn group rats compare pulmonary artery systolic blood pressure increased significantly with the Cn group (P<0.01);Ti group compared with Cn group of pulmonary artery systolic pressure had no statistical difference (P>0.05); Co grup compared with Cn group had no statistical difference (P>0.05). Tn group compared with Cn group from activity of NF-KB had increased significantly (P<0.01); Ti is Cn group significantly decreased (P<0.01);Had no statistical difference between Co and Cn group (P>0.05). Tn group rats ADM and PGI2expression is Cn reduce, Ti and Cn group had no significant difference; compared Co group with Cn GROUP had no significant difference.Conclusion:High blood pulmonary vascular remodeling and pulmonary artery pressure is related to the activity of nf-kappa B; The activity of nf-kappa B groups, Measured the expression of vascular active substances ADM and PGI2is reduced,After applying the nf-kappa B blockers PDTC can inhibit the activity of nf-kappa B, obstruct pulmonary vascular remodeling, inhibition of pulmonary hypertension.