Clinical Analysis For Risk Factors Of Rheumatoid Heart Valvular Disease-induced Pulmonary Hypertension Effects Of Iptakalim On The LPS-induced Muc5AC Overproduction Of Human Airway Epithelial Cell

Objective Rheumatoid heart disease is the most common cause of cardiovascular diseases in polulation under25years. Reports show rheumatoid heart disease is a very common reason in causing heart valvular diseases. Pulmonary hypertension (PH) is a common and severe disease, with worse prognosis, higher disability rate and mortality. Thus paying attention on left heart valvular disease, deepening the understanding of pulmonary hypertension, reducing the rate of disability rate and mortality is becoming more and more important. This article analyses the clinical data of rheumatoid valvular heart disease, and investigate the risk factors associated with such type of PH, offering evidence for an earlier intervention and a better prognosis.Methods Through investigating basic clinical characteristics such as medical history, sign, echocardiograph results and so on before surgery, we analyzed256rheumatoid valvular heart disease patients with intact clinical data. Echocardiograph was used to assess their pulmonary pressure. They were divided into non-PH group (n=157,<35mmHg), suspected PH group (n=50,35～50mmHg) and PH group (n=49,>50mmHg). Different statistical methods including multiple regressive analysis were employed to analyze differences between those patients with PH and those without PH.Results The average age of rheumatoid valvular heart disease patients complicated with PH was50.2. The ratio of male to female was18:31. Higher heart function grade of New York Heart assiociation (NYHA)(OR=1.243), bigger left atrial diameter (LAD)(OR=1.016) and the longer duration of heart failure (OR=1.018) were the risk factors of PH in rheumatoid valvular heart disease patients. Conclusions Rheumatoid valvular heart disease is an important cause of PH. The difference is significant between PH patients and non-PH patients as to body mass index (BMI), NYHA, LAD and the duration of heart failure and atrial fibrillation. The patients with higher heart function grade of NYHA, larger LAD, longer duration of heart failure are more likely to develop PH. Objective:Mucus overproduction is an important feature of chronic airway disorder. If left untreated, it will worsen the prognosis of diseases, contributing to its mobility and mortality. The related mechanism underlying this and the treatment is arousing more and more attention. Our study administer lipopolysaccharides to induce mucus hypersecretion, thus providing a way for us to observe ATP sensitive potassium channel opener (KATPCO, KATp channel opener) iptakalim (IPT)’s role in decreasing the oversecretion of human airway epithelial cells.Methods:We culture human bronchial epithelial cell line (16HBE), divide them into four groups:control group, LPS (10μg/ml) group, LPS (10μg/ml)+IPT,(10μM) group and IPT (10μM) group. After the cells reach60%-70%confluence,the cells were serum starved overnight, we predispose cells to iptakalim or not, then we give LPS (10μg/ml) half an hour later. Then we collect cell or permeate them, use different methods such as realtime-PCR to detect muc5ac gene level, fluorescence microscope for reactive oxygen species level, luminoscope for extracellular and intracellular ATP level, western blot for CAMKⅡ, ERK phosphorylation level.Results:After administering LPS for24hours, LPS can upregulate muc5ac gene expression. Different doses of IPT (10、1、0.1μM) were given, only10μM of IPT reduced the mu5ac expression. LPS can increase intracellular ROS level, stimulate ATP release, induce phosphorylation of CAMKⅡ and ERK. After giving IPT (10μM), intracellular ROS level, extracellular ATP level were reduced. Also it can reverse the phosphorylation of CAMKⅡ and inhibit the phosphorylation of ERK. Conclusion:IPT (10μM) decreases intracellular ROS level, extracellular ATP level. It can reverse the phosphorylation of CAMKII and inhibit the phosphorylation of ERK, thus reducing muc5ac expression, alleviating muc5ac overexpression induced by inflammation.