模拟高原低氧环境下大鼠肺组织PGC-1α、ERRα的表达变化  

Expression changes of PGC-1α and ERRα in rat lung tissue under simulated high altitude hypoxia environment

作　　者：李艳[1] 罗晓红[1] 冯小明[2] 牛小娟 周珺[3] 哈小琴[4] 刘斌[5] 牛廷献 Li Yan;Luo Xiao-hong;Feng Xiao-ming;Niu Xiao-juan;Zhou Jun;Ha Xiao-qin;Liu Bin;Niu Ting-xian(Department of Endocrinology,The 940th Hospital of Joint Logistics Support Force of People's Liberation Army,Lanzhou 730050,China;Department of Animal Experiment,The 940th Hospital of Joint Logistics Support Force of People's Liberation Army,Lanzhou 730050,China;Department of Pharmacy,The 940th Hospital of Joint Logistics Support Force of People's Liberation Army,Lanzhou 730050,China;Department of Laboratory,The 940th Hospital of Joint Logistics Support Force of People's Liberation Army,Lanzhou 730050,China;Department of Pathology,The 940th Hospital of Joint Logistics Support Force of People's Liberation Army,Lanzhou 730050,China)

机构地区：[1]中国人民解放军联勤保障部队第九四○医院内分泌科,甘肃兰州730050 [2]中国人民解放军联勤保障部队第九四○医院动物实验科,甘肃兰州730050 [3]中国人民解放军联勤保障部队第九四○医院药剂科,甘肃兰州730050 [4]中国人民解放军联勤保障部队第九四○医院检验科,甘肃兰州730050 [5]中国人民解放军联勤保障部队第九四○医院病理科,甘肃兰州730050

出　　处：《兰州大学学报（医学版）》2021年第6期35-40,共6页Journal of Lanzhou University（Medical Sciences）

基　　金：甘肃省自然科学基金资助项目(1606RJZA173)。

摘　　要：目的探讨在高海拔低氧环境下随着缺氧时间的变化,大鼠肺组织中PGC-1α、ERRα的表达情况。方法选取雄性Wistar大鼠32只,随机分为对照组、缺氧组,缺氧组进一步分为缺氧6 h、12 h、24 h组,每组8只大鼠。对照组置于常氧环境下(海拔1 500 m),缺氧组置于低压氧舱(6 500 m)模拟高原缺氧环境,建立高原肺水肿大鼠模型。光学显微镜下观察大鼠肺组织病理改变。分光光度法检测大鼠肺组织匀浆CAT、SOD、GSH-PX、MDA活性。qRT-PCR法、Western blotting法检测各组大鼠PGC-1α、ERRαmRNA及蛋白表达。结果大鼠肺脏HE染色显示对照组肺组织结构清晰,未见肺水肿;缺氧组肺泡腔显著扩张,肺泡间隔增宽,肺纹理紊乱,随着缺氧时间的延长,肺组织损伤愈严重,并且逐渐出现红细胞及少量中性粒细胞浸润。氧化应激指标CAT、SOD、GSH-PX的活性随着缺氧时间延长逐渐下降,MDA逐渐增高,表明肺水肿模型建造成功。肺组织PGC-1αmRNA和蛋白表达在缺氧6 h、12 h组表达增高,差异具有统计学意义(P <0.01或P <0.05);ERRαmRNA及蛋白表达在缺氧不同时间点均呈下降趋势,差异具有统计学意义(P<0.01或P<0.05)。结论 PGC-1α在高海拔低氧条件下被激活,且呈现时间依赖性,而ERRα表达被抑制。PGC-1α/ERRα可能参与高原肺水肿的发生发展,通过调节PGC-1α、ERRα可能为高原肺水肿的治疗提供新的思路。Objective To explore the expression of PGC-1 α and ERR α in rat lung tissue with the changes in hypoxia time at a high altitude and hypoxia. Methods 32 male Wistar rats were randomly divided into the control group and the hypoxia group. The rats were further divided into hypoxia groups of 6 h, 12 h and24 h, with 8 in each group. The control group was exposed to normoxic environment(1 500 m altitude),the hypoxia group was placed in a hypobaric oxygen chamber(6 500 m) to simulate high altitude hypoxia environment to establish a rat model of high altitude pulmonary edema. The pathological changes of lung tissue were observed under light microscope. The activities of CAT, SOD, GSH-PX and MDA in lung homogenates of rats were detected by spectrophotometry. The expressions of PGC-1α and ERRα mRNA and protein were detected by qRT-PCR and Western blotting methods. Results HE staining of rat lungs showed that the lung tissue structure of the control group was clear, and no pulmonary edema observed. In the hypoxic group,the alveolar cavity was significantly expanded, alveolar interval was widened, and lung texture was disordered, with a severe and gradual infiltration of red blood cells and a small amount of neutrophils. Oxidative stress indicators CAT, SOD, GSH-PX activity gradually decreased with the extension of hypoxia time,and MDA gradually increased, indicating that the pulmonary edema model was successfully constructed.Lung tissue PGC-1α mRNA and protein expression increased at 6 hours and 12 hours of hypoxia, the difference was statistically significant(P < 0.01 or P < 0.05);ERR α mRNA and protein expression showed a downward trend at different time points of hypoxia, and the difference was statistically significant(P < 0.01 or P < 0.05). Conclusion PGC-1α was activated at high altitude and hypoxia in a time dependent manner, and the expression of ERR α was inhibited. PGC-1 α might be a potential therapeutic target for high-altitude pulmonary edema.

关 键 词：高原肺水肿 过氧化物酶体增殖物受体辅助激活因子-1α 雌激素相关受体α 

分 类 号：R563[医药卫生—呼吸系统]