对照组在常氧环境中饲养，连续21 d。观察小鼠体征。末次低氧暴露后检测2组小鼠心乳酸脱氢酶（LDH）、Na+-K+-ATP酶活性，肺功能变化，心、肺组织缺氧诱导因子-1α（HIF-1α）及肺组织通道蛋白-5（AQP5）蛋白和基因表达。结果 模型组小鼠出现气虚体征。与对照组比较，模型组小鼠心LDH活性增高、Na+-K+-ATP酶活性降低（P<0.05，P<0.01）；肺功能指标检测结果显示，模型组小鼠吸气时间、呼气时间、持续时间、潮气量、呼气末端停顿均降低和频率升高（P<0.05，P<0.01）；心、肺HIF-1α蛋白、基因表达均增高，肺AQP-5基因表达增高（P<0.05，P<0.01）。结论 较长时间的高原低氧暴露，可导致小鼠表现气虚体征并出现肺通气效率降低。心肌受损可能与心Na+-K+-ATP酶活性变化有关，而心、肺HIF-1α表达及肺AQP-5基因表达升高，可能有利于提高心、肺的适应性代偿反应。
关键词：高原低氧暴露；气虚；乳酸脱氢酶；钠-钾-ATP酶；缺氧诱导因子-1α；水通道蛋白-5；小鼠
DOI：10.3969/j.issn.1005-5304.2015.12.013
中图分类号：R223；R228 文献标识码：A 文章编号：1005-5304（2015）12-0050-05
Study on Molecular Mechanism of Reactive Changes in Heart and Lung of Mice in High Altitude Hypoxia LUO Ya-li1，2， LIU Yong-qi1，2， AN Fang-yu3， SUN Li-jiao4， CAI Lu-lu4， LI Xin4， MA Yan-ping4 （1.Key Laboratory for Molecular Medicine of Major Diseases and Prevention and Treatment with Traditional Chinese Medicine Research at Provincial Level， Gansu University of Chinese Medicine， Lanzhou 730000， China；2.Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level， Lanzhou 730000， China；3.Experimental Teaching Center， Gansu University of Chinese Medicine， Lanzhou 730000， China；4.College of Public Health， Gansu University of Chinese Medicine， Lanzhou 730000， China）
Abstract：Objective To discuss the molecular mechanism of reactive changes in heart and lung of mice models in high altitude hypoxia environment. Methods Healthy SPF mice were put in hypoxia cabin for decompression and hypoxia exposure to make model， and mice in the control group were fed in normoxia environment for 21 days. The physical signs of the mice were observed. After the last time of hypoxia exposure， mice were detected for indexes of correlation along with the control group. LDH， Na+-K+-ATPase activities of heart， changes of pulmonary function， and gene and protein expression of HIF-1α in the heart and lung tissue， AQP-5 in the lung tissue were detected. Results Mice in the model group showed signs of qi deficiency. Compared with the control group， Na+-K+-ATPase activity of heart tissue was lowered （P<0.01） but LDH was raised significantly （P<0.05） in the model group. The detection results of pulmonary function displayed that the indexes such as Ti， Te， RT， EEP and TV were all dropped （P<0.05 or P<0.01） in the model group. However， the respiratory frequency increased significantly. The gene and protein expressions of HIF-1α in heart and lung all increased （P<0.05 or P<0.01） in the model group.
