The Pathogenesis Of The Pulmonary Artery Hyper Tension Related Obstructive Sleep Apnea-hyponea Syndrome And The Effects Of Rho/Rho-kinase Signaling Pathway In Its And The Intervention Effects Of Fasudil On Its

Objective:To study the relationship between pulmonary artery hypertension (PAH) related obstructive sleep apnea-hyponea syndrome (OSAHS) and clinical relative factors; and then investigate the pathogenesis of PAH related OSAHS and the effects of Rho/Rho-kinase signaling pathway in this pathogenesis. Finally detect the intervention effects of Fasudil on this pathogenesis.Methods:Part1.17OSAHS patients with PAH were set as study group, and while another17random OSAHS patients without PAH were set as control group. All of the patients were treated with polysomongram (PSG) detecting during night, detecting artery blood gas analysis in the morning, pulmonary function test and pulmonary artery pressure by Doppler ultrasound.Part2.17random OSAS patients without PAH were set as control group, and while another17random severe OSAHS patients with PAH were set as study group. Ulnar venous blood was used to detect IL-6、TNF-α、hs-CRP, ADM, ET-1and VGEF when patients were fasting in the morning; and also the levels of Rho A、ROCK-Ⅱ in blood serum were evaluated. At last, FMD and MT were estimated Doppler ultrasound.Part3.17patients in study group were study objects.30mg fasudil hydrochloride was pumping12h a time during15d, and after these days, levels of ADM, TNF-a, ET-1and Rho A were evaluated. The concentrations of ADM in blood plasma and Rho A in blood serum were detecting in3,7and15d during treatment. Then blood gas analysis, PSG detecting and Borg classification scores of6min walking test were proceeded.Results:Part1. They had no significantly different between the two groups in age, Mallampati classification, BMI, PaCO2, FVC and FEV1/FVC (P>0.05). PAH related OSAHS had positive correlation with AHI and TS90%, but negative correlation with LSaO2and PaO2, and there were significantly different between the two groups in the four factors of AHI, TS90%, LSaO2and PaO2(P<0.01)Part2. There were significantly different between the two groups in IL-6, TNF-α and hs-CRP; Some detecting targets such as ADM, ET-1, ET-1/NO, VEGF increased, but NO decreased; Rho A, ROCK-Ⅱ had significantly different between the two groups, and pulmonary artery pressure had positive correlation with Rho A and ROCK-Ⅱ.Part3. ADM, TNF-a, ET-1, Rho A, TS90%and PAPm decreased significantly after treatment. However, LSaO2and PaO2increased significantly after treatment. ADM and RhoA reduced from the third day (P<0.05), and they decreased significantly at the seventh day and the fifteenth day after treatment (P<0.01). They would reduce2-4degree of Borg classification (P<0.05), and walking distance was also extended (P <0.05)Conclusions:1. PAH related OSAHS is influenced by many clinical factors and assessed by means of the variations of these factors before operation;2. The pathogenesis of PAH related OSAHS has correction with oxidative stress and local/systemic inflammatory reaction, constriction and reconstruction of pulmonary vascular, and the pathway of Rho/ROCK signal transduction.3. Fasudil has effect on the pathway of Rho/ROCK signal transduction, decreases PAH, and improves patient oxygenation and hyoxemia.