| Background:With the advance of global economy and transportation network, the population composition in plateau has changed more, which an increasing number of people from low, altitude areas has chose to reside in plateau. HAPC is a serious harm to people’s health and major diseases plateau diseases. The HAPC of red blood cell increased blood viscosity, excessive blood flow resistance increases, oxygen content decreased, showing as the occurrence of the following symptoms and signs, such as headache, dizziness, heart palpitations, gastrointestinal discomfort, chest tightness, memory loss and abnormal sensation,which will lead to high altitude pulmonary hypertension, heart disease and other plateau chronic high altitude disease(chronic mountain sickness, CMS) trend; severely affect quality of life and work efficiency, and increased with the incidence of plateau seriously affected the improvement of combat troops or influence economic construction process in Plateau area. Therefore, to explore the factors associated with the onset of HAPC, and then discusses its possible pathogenesis, prevention and treatment of chronic mountain sickness research guide will have important theoretical value and practical significance.Plateau hypoxia, tissue hypoxia caused by excessive increase in the number of red blood cell is the root cause of HAPC, but its inherent physiological and pathological changes, it is not clear. Several reports had confirmed that an increasing expression of hypoxia inducible factor-1α(HIF-1α), relating with several regulating factors, can lead to excessive erythropoiesis according to promoting the secretion of Erythropoietin(EPO), induce red blood cell hyperplasia, cause the inflammatory reaction, and ultimately lead to the occurrence of HAPC, blood flow, viscous resistance increases, aggravating hypoxia.The body organ group long-term hypoxia, the intracellular superoxide dismutase(SOD), oxygen free radical, catalase(CAT) activity increased, and lactic acid(LA), hydrogen peroxide(H2O2) levels, damage the body micro environmental balance, the red cell edema, degeneration, dissolution, apoptosis inflammatory reaction. Therefore, the present study suggests that inflammatory cytokines may play an important role in the occurrence and development of HAPC.Cytokine was a kind of cytokine in the inflammation process released by the cells or produced.A protein microarray, according to encoded probe to catch specific protein molecules in solid phase carrier, is a tool used to confirm biological information and conduct biochemical analysis, possessing the characters of high sensitivity and high throughput measurements. With the help of reviewing a number of related studies, our research has chosen the relative inflammatory cytokines, and then detected the expression changes of these inflammatory cytokines in serum of HAPC patients using the protein microarray technique. By means of these, our study aime to explore the possible interaction mechanism between inflammatory cytokines and other cytokines such as EPO, HIF-1α and androgen receptor(AR), and were expected to get the valuable molecular markers to provide theoretical basis for the preparation of protein microarray using in clinical diagnosis.Methods:1.The health reports from the male soldiers, who have been migrating in Qinghai-Tibet Plateau for 10 months between May 2010 and Match 2013, were collected to explore the risk factors of HAPC, as well as the relative clinical data.2.A second physical examination was conducted among the suitable volunteers in Tibet shannan district for 1 year or more for protein microarray test. Ten of the volunteers who were diagnosed based on Qinghai criteria( HGB≥210 g/L) were classified as HAPC group, other ten volunteers(150≤HGB<190g/L) were classified as control group. In addition, peripheral blood serum was collected as the sample for protein microarray test.3.The preparation of protein microarray: 40 inflammatory cytokines, relating with CMS, were chose as the suitable markers. The blood serum samples of HAPC group and control group were detected.4.EPO, HIF-1a, AR and the possible discrepant inflammatory cytokines based on the protein microarray test were analyzed in STRING9.1 database. According to the construction of protein-protein interaction networks and the relevant analysis, the possible mechanism was further explored.Results:1.There were 105 HAPC patients present in 546 Han male migration residents, and the relative prevalence was 19.2%. Significant correlations emerged between the altitude, the dwelling time, smoking and the prevalence(p< 0.05), as well as BMI index when the age ≥34.2.The indicators, such as HGB values, dwelling times, BMI index, clinical symptom scores, were apparently higher than the health people in the same plateau, in contrast, the reverse outcome was received in SpO2 comparison. In addition, there was no statistical significant in age, heart rate, and blood pressure comparison. According to the logistic regression analysis, the risk factors for HAPC were showed as the following in order: smoking, altitude, dwelling time, and BMI index. SpO2 was regarded as a protected factor.3.7 inflammatory cytokines, including IL-1β、IL-2、IL-3、IL-15、IL-16、MCP-1/CCL2、TNF-α/LTA, displayed a higher expression in the blood serum of HAPC patients(P<0.05).4.Ten kinds of cytokines evolutionary tree and the graph of protein-protein interaction networks were got according to STRING9.1 database.Conclusion:1.The occurrence and progression of HAPC among the Han male migration residents have related with the altitude, dwelling time, BMI index, smoking, and SpO2, which could be regarded as clinical evidence.2.IL-1β、IL-2、IL-3、IL-15、IL-16、MCP-1/CCL2、TNF-α/LTA involved in the inflammatory response of the occurrence and progression of HAPC.3.Protein-protein interaction networks showed significant correlations between AR、EPO、HIF-1a and cytokines such as MCP-1、TNF-α、IL-1β、IL-2、IL-3、IL-15、IL-16, which provides a new clue for exploring the pathogenesis of HAPC as well as the prevention. |
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