The Clinical Effect Of Rho-kinase In Blood In Patients With Chronic Obstructive Pulmonary Disease

BackgroundChronic obstructive pulmonary disease is a kind of important chronicrespiratory disease, High morbidity, high mortality. Due to its slow progressivedevelopment, which seriously impact the patients’ ability to work and the quality oflife. Patients with COPD in after acute episode, though they have clinical symptomrelief, but the lung function is still in continue to deteriorate, and because of its owndefense and immune function of lower and external various harmful factors, oftenrepeated attacks, and gradually produce all kinds of cardiopulmonary complications.The world health organization said, chronic obstructive pulmonary disease canprevent, but there is no cure. Therapy help slow the progress of the disease, but thedisease usually in a period of time after gradually deteriorated. Airway inflammationis the starting point of COPD, airway remodeling is the pathology base airflowobstruction COPD, COPD is the key factor for disease. Therefore, and study thepathological changes and happened to improve the control effect mechanism and theprognosis of patients with to have the important meaning. An important complicationof Chronic obstructive pulmonary disease is an important complication pulmonary hypertension, chronic obstructive pulmonary disease with pulmonary hypertension ishappening and slow progress gradually, pulmonary hypertension is chronicobstructive pulmonary disease development to the importance of cor pulmonalepathological physiology process, if pulmonary artery pressure continue to rise, canlead to right heart load increasing, which eventually led to the right heart failure.Research shows that Rho/Rho kinase signaling pathway is a signaltransduction pathway common body tissue，The path of the key signaling moleculesincluding: Rho protein, Rho kinase and Myosin phosphatase. Its through regulatingcell actin skeleton polymerization state, participate in the cells form maintain control,cell adhesion and migration, the cell proliferation and apoptosis, gene transcription,smooth muscle contraction and so on many kinds of biological behaviour, mediated avariety of smooth muscle and the smooth muscle function abnormal related thehappening of the disease mechanism. In a variety of diseases in animal model smoothmuscle cells Rho kinase there are too many of the expression. Rho/Rho kinase signalpathway involved in the pathogenesis of COPD process, Rho kinase inhibitors inhibitinflammatory cells migration and the chemotaxis, antagonist inflammatory factorsecretion, blocking the inflammatory factor effect, to play the anti-inflammatoryeffects, improve the airway remodelling.In this study, the expression changes of the serum of Rho kinase1(ROCK1) inthe Rho/Rho kinase signaling pathway in patients with chronic obstructivepulmonary disease (COPD) and COPD associated with pulmonary arterialhypertension (PAH),, provide the basis for the prevention and treatment COPDofCOPD and concomitant pulmonary hypertension provide new therapeutic targets.ObjectiveDetected by enzyme-linked immunosorbent assay (ELISA) and cells Flowcytometry technology to detect the normal population and the chronic obstructivepulmonary disease (COPD) associated or not associated with pulmonary arterialhypertension (PAH) of patients with serum and peripheral blood of mononuclear cells Rho kinase1(ROCK1) expression changes, From pathogenesis to explore therole of Rho/Rho kinase signaling pathway in COPD associated or not associatedwith pulmonary arterial hypertension (PAH) of patients.Methods1. Object of studyCollected in January2010~January2011COPD patients admitted to Hedongbranch in Guangzhou First Municipal People’s Hospital,40cases including20casesof patients with COPD,20cases of patients with COPD associated with pulmonaryarterial hypertension (PAH), in which patients with COPD groupmeet the diagnosticcriteria for chronic obstructive pulmonary disease treatment guidelines developed in2007by the Chinese Society of Respiratory Branch; with COPD with associatedpulmonary hypertension group at the same time meet the diagnostic criteria forchronic obstructive pulmonary disease treatment guidelines developed in2007by theChinese Society of Respiratory Branchdiagnostic criteria the ESC2009years todevelop pulmonary hypertension diagnosis and treatment guidelines. In another20cases of hospital medical center healthy persons as control group. Three groups in theage, sex, weight as far as possible on the match.2. Pulmonary function testAll of the subjects required to pulmonary function testing, the major indexes,including forced vital capacity (FCV), first second forced expiratory volume (FEV1),FEV1/FVC ratio and FEV1percentage of predicted value (FEV1%)，FEV1/FCVafter inhalation of a bronchodilator (salbutamol400ug).3.Determination of the mean pulmonary arterial pressureDetermination of mean pulmonary arterial pressure (mPAP) in the quiet state ofall subjects by cardiac color ultrasoundcolor examination.4. The serum ROCK1expression level detection4.1Specimen collection: extract the object of study for fasting blood3ml,centrifugation (3000R/15min.20°C), specimens from the upper serum1ml, Save the test in the refrigerator, the temperature is set to low temperature-80°C4.2Measurement methods: the detection of serum the ROCK1the expressionlevel of the enzyme-linked immunosorbent assay (ELISA), which sample preparation,determination and sample concentration calculations are in accordance with therelevant kit instructions.5. Peripheral blood mononuclear cells ROCK1expression level detection5.1.Sample collection: fasting blood20ml extraction study, monocytes isolatedby Improved Ficoll-Hypaque density separation and plastic adsorption methodsedimentation, Save the test in the refrigerator, the temperature is set to lowtemperature-80°C5.2Measurement methods: flow cytometry study from peripheral bloodmononuclear cells the ROCK1the expression level. Which the specimen processing,determination of methods and sample concentration calculations are carried out inaccordance with the instructions of the relevant kit.Results1.Serum ROCK1expression levels in the control group, the COPD group withCOPD associated with PAH group were13.10±2.67,23.55±4.97and36.72±7.18pmol/L, and the COPD group with COPD associated with PAH group wassignificantly higher. Among the three groups there were significant differences (P<0.01).2. peripheral blood mononuclear cells ROCK1expression level in the control group,COPD group, COPD associated with PAH group were3.61±2.44,10.56±3.72and31.21±8.83%, statistic analysis showed significant differences between the threegroups (P <0.01).3.the relevance of the subjects serum ROCK1levels and mean pulmonary arterypressure was positively correlated (r=.654, P <0.05), peripheral blood mononuclearcells ROCK1expression levels and pulmonary artery mean pressure was alsopositively correlated (r=0.664, P <0.05), serum ROCK1level of peripheral blood mononuclear cells ROCK1expression levels were significantly positively correlated(r=0.864, P <0.01).ConclusionActivation of Rho/Rho kinase signaling pathway involved in the formation anddevelopment of COPD disease pulmonary arterial hypertension, elevated serumROCK1expression may be related with the high expression of ROCK1in monocytes.