目的:高原肺水肿严重影响高原人群的健康。筛选高原肺水肿易感基因以用于高原肺水肿易感者的评估及防护。方法:利用Affymetrix SNP Array 6.0芯片对23例高原肺水肿患者和17个健康对照进行全基因组SNP分型,利用PLINK软件进行了全基因组关联分析,利用GO和Pathway软件进行分析及作图。结果:全基因组关联分析获得39个相对显著的SNPs位点(P<10-4)。通过对这些SNP位点附近27个基因的GO和Pathway富集分析,发现这些基因主要参与细胞增殖调控过程、氮代谢过程和G蛋白耦联受体蛋白信号转导通路等。结论:本文发现的多态性位点及相关基因可能与高原肺水肿易感性相关。
Objective To investigate the effects of simple hypobaric hypoxia on parameters of hematology and blood rheology in order to establish a rat model of simulated high altitude polycythemia(HAPC) for the study of pathophysiologic mechanisms and medical prevention and treatment of HAPC.Methods Fortyeight male Wistar rats were randomly divided into three normal control groups and three hypoxia model groups.Normal control group rats were bred in normoxia conditions,and hypoxia group rats were subjected to hypoxic exposure for 8 hours per day at simulated 5 500 m high altitude in a hypobaric chamber.After hypoxic exposure for 2,4,12 weeks,one group of normal control and hypoxia model rats were killed and blood was collected,respectively.Then parameters of erythrocyte and blood rheology were examined.Results Mucous membrane of hypoxia model rats showed obviously cyanosis after 2 weeks hypoxic exposure.Hemoglobin concentration of hypoxia model rats were beyond 210 g/L after 2 weeks,4 weeks and 12 weeks hypoxia exposure and significantly increased than that of normal control rats respectively.Besides,RBC counts,hematocrit,whole blood viscosity,erythrocyte aggregation index of hypoxia model rats were all notably higher than those of normal control rats respectively.Conclusion A rat model of high altitude polycythemia can be rapidly established by hypobaric hypoxia exposure at simulated 5 500 m high altitude for 8 hours daily.
Pei-bing LIHong-jing NIEWei LIUBing-nan DENGHui-li ZHURui-feng DUANZhao-li CHENHai WANG
Vascular endothelium plays an important role in regulating vascular homeostasis. Over the past years, it has become clear that endothelial dysfunction is a key event of pathophysiological changes in the initiation and progression of injuries induced by extreme environmental factors. The present review summarizes current understanding of vascular endothelial dysfunction induced by hypoxia, cold and heat, and provides the information for prevention and treatment of environmental exposure injuries.
Wei LIUJia-ying LIUZhao-yun YINChao-liang LONGHai WANG
Objective High altitude pulmonary edema(HAPE), a life-threatening disease, has no biological markers used for the routine prevention, diagnosis and treatment. The aim of this study was to identify serum proteins differentially expressed in patients with HAPE for discovering essential biomarkers. Methods A complete serum proteomic analysis was performed on 10 HAPE patients and on 10 high altitude and 11 sea level healthy people as control using two-dimensional gel electrophoresis, followed by matrixassisted laser desorption/ionization mass spectrometry and peptide mass fingerprinting. Finally, two most significantly changed proteins were validated by enzyme-linked immunosorbent assay(ELISA). Results Eight protein spots stained with differential intensity, respresenting 5 distinct proteins were identified in patients compared with healthy controls through analysis of these composite gels. Among them, four proteins, namely alpha 1-antitrypsin(α1-AT), Haptoglobin(Hp), apolipoprotein A-I(apoA-1) and Complement C3 increased remarkably, while one protein, apolipoprotein A-IV(apoA-IV) decreased significantly. The variation of α1-AT and Haptoglobin, as detected by ELISA, was consistent with the results from proteomic analysis. Conclusions It is well known that Hp, α1-AT and complement C3 are associated with inflammation and apoA-1 and apoA-IV play important roles in lipid absorption, transport and metabolism. Therefore, the significant expression changes of Hp, α1-AT and complement C3 and apoA-1 and apoA-IV between HAPE patients and their corresponding healthy controls highlight the role of inflammatory response system and lipid metabolism system in the pathophysiology of HAPE.
Yuan-yuan ZHANGRui-feng DUANWen-yu CUIZhi-yuan PANWei LIUChao-liang LONGYin-hu WANGHai WANG
