不同海拔下大鼠肺组织中EGLN1基因的表达及其与肺动脉压的相关性  

Correlation between EGLN1 gene, protein express in lung tissue of rats and pulmonary artery pressure at different altitude

作　　者：李生花[1] 李胜[3] 孙莉[1] 白振忠 杨全余 嘎琴 靳国恩 

机构地区：[1]青海大学医学院基础医学部,西宁810001 [2]高原医学研究中心青海省高原医学应用基础重点实验室 [3]青海省地方病预防控制所

出　　处：《中华医学杂志》2016年第32期2592-2597,共6页National Medical Journal of China

基　　金：国家自然科学基金（81160243,81550040）;青海省留学回国人员科技活动项目（青人社厅函[2011]518号）

摘　　要：目的探讨不同海拔下大鼠肺组织中Eg1九同源物1（EGLN1）基因表达及其与平均肺动脉压（mPAP）的相关性。方法121只雄性Wistar大鼠用随机数字表法随机分为低海拔组（11只）、中海拔组和高海拔组，后两组又各分为低氧第1、3、7、15和30天5小组，每小组11只。低海拔组于498m地区进行生理信号采集和组织样本的收集，中海拔组置于2260m自然环境，高海拔组置于低压氧舱，模拟海拔为4500m。中海拔组和高海拔组在低氧暴露第1、3、7、15和30天进行生理信号采集和组织样本的收集。用生理信号采集系统测定mPAP；Western印迹法测定肺组织EGLNl蛋白表达水平，用Pearson相关性分析其蛋白是否与低氧下肺动脉高压的形成有关；用实时定量-PCR测定肺组织EGLN1 mRNA水平，用2^-△△ct倍数法分析PCR数据，评估低氧下EGLN1基因是否为肺动脉高压形成的初始原因。结果低海拔组mPAP为（20．0±3．2）mmHg（1mmHg=0．133kPa）；中海拔组mPAP于第15天开始有所升高，第30天为（22．7±4．1）mmHg，但与低海拔组差异无统计学意义（P〉0．05）；高海拔组mPAP于暴露低氧第7天[（28．7±7．7）mmHg]就显著高于低海拔组（P〈0．05），第30天[（42．3±9．1）mmHg]升高更明显（P〈0．001）。高海拔组EGLN1蛋白表达水平随暴露低氧时间的延长而逐渐下降，且均显著低于低海拔组和中海拔组（均P〈0．05），EGLN1蛋白表达水平与mPAP呈负相关（r=-0．662，P〈0．05）。高海拔组EGLN1 mRNA表达水平显著升高，是中海拔组的72倍和低海拔组的近300倍（均P〈0．001）。结论大鼠肺组织EGLN1基因表达随海拔升高而升高；但其蛋白水平却相反，并与mPAP呈负相关。Objective To investigate the correlation between pulmonary artery pressure （PAP） and the expression level of Egl nine homologue 1 （EGLN1） gene or its protein in lung tissue of rats at different altitudes. Methods Totally 121 male Wistar rats were randomly divided into low altitude group （n = 11 ）, moderate altitude group and high altitude group, the rats in moderate altitude and high altitude group were further divided into 1 st day, 3rd days, 7th days, 15th day and 30th day group according to the exposure time to hypoxic environment, each group 11 rats. The low altitude group, the PAP of rats were determined by physiological signal acquisition system, and tissue samples were collected in liquid nitrogen container for storage at an altitude of 498 m area. Moderate altitude group rats were placed in altitude of 2 260 meters of natural environment, 5 high altitude groups rats were placed in the hypobaric hypoxic chamber, simulating altitude of 4 500 meters. The PAP of rats in moderate altitude group and high altitude group were also determined by physiological signal acquisition system, and tissue samples were collected when rats were exposed to hypoxia at 1st, 3rd, 7th, 15th and 30th day; Western blot was used to determine expression levels of EGLN1 protein, and person correlation analysis was used to analyze whether the protein was related to the formation of pulmonary arterial hypertension （PH） under hypoxia. Real-time quantitive PCR method determined expression levels of EGLN1 mRNA in lung tissues, and the relative expression method was used to analyze PCR data, and finally assess whether the EGLN1 gene was the initial cause of the formation of PH during hypoxia. Results The mean PAP of rats was （20. 0 ±3.2） mmHg （ 1 mmHg = 0. 133 kPa） in low altitude group; in moderate altitude group, mean PAP began to increase slightly when rats were exposed to hypoxia on the 15th day and reached at （22. 7 ±4. 1 ） mmHg on hypoxic 30th day, but compared with the low altitude group, there was no st

关 键 词：高血压 肺性 高海拔 EGLN1基因 大鼠 

分 类 号：R544.1[医药卫生—心血管疾病]