Yuhong Li, Zhengzhong Bai, Feng Tang, Quanyu Yang, Ge Ri-Li
Research Center for High Altitude Medicine; Key Laboratories Development Program of Qinghai Province; and Qinghai-Utah Joint Research Key Lab for High Altitude Medicine, Qinghai University, Xining, China; Department of Respiratory Medicine, the Affiliated Hospital of Qinghai University, Xining, China.
Research Center for High Altitude Medicine; Key Laboratories Development Program of Qinghai Province; and Qinghai-Utah Joint Research Key Lab for High Altitude Medicine, Qinghai University, Xining, China.
Wilderness Environ Med. 2017 Dec;28(4):285-290. doi: 10.1016/j.wem.2017.05.009. Epub 2017 Jul 21.
Chronic hypoxia-induced pulmonary hypertension and vascular remodeling have been shown to be associated with ornithine decarboxylase 1 (ODC1). However, few animal studies have investigated the role of ODC1 in acute hypoxia.
We investigated ODC1 gene expression, morphologic and functional changes, and the effect of L-arginine as an attenuator in lung tissues of rats exposed to acute hypobaric hypoxia at a simulated altitude of 6000 m.
Sprague-Dawley rats exposed to simulated hypobaric hypoxia (6000 m) for 24, 48, or 72 hours were treated with L-arginine (L-arginine group, 20 mg/100 g intraperitoneal; n=15) or untreated (non-L-arginine group, n=15). Control rats (n=5) were maintained at 2260 m in a normal environment for the same amount of time but were treated without L-arginine. The mean pulmonary artery pressure was measured by PowerLab system. The morphologic and immunohistochemical changes in lung tissue were observed under a microscope. The mRNA and protein levels of ODC1 were measured by real-time polymerase chain reaction and Western-blot, respectively.
Hypobaric hypoxia induced pulmonary interstitial hyperemia and capillary expansion in the lungs of rats exposed to acute hypoxia at 6000 m. The mean pulmonary artery pressure and the mRNA and protein levels of ODC1 were significantly increased, which could be attenuated by treatment with L-arginine.
L-arginine attenuates acute hypobaric hypoxia-induced increase in mean pulmonary artery pressure and ODC1 gene expression in lung tissues of rats. ODC1 gene contributes to the development of hypoxic pulmonary hypertension.
慢性缺氧诱导的肺动脉高压和血管重塑已被证明与鸟氨酸脱羧酶1（ODC1）有关。然而，很少有动物研究调查ODC1在急性缺氧中的作用。
我们研究了ODC1基因表达、形态和功能变化，以及L-精氨酸作为一种衰减剂对暴露于6000米模拟海拔急性低压缺氧大鼠肺组织的影响。
将Sprague-Dawley大鼠暴露于模拟低压缺氧（6000米）24、48或72小时，分别用L-精氨酸处理（L-精氨酸组，腹腔注射20毫克/100克；n = 15）或不处理（非L-精氨酸组，n = 15）。对照大鼠（n = 5）在正常环境中维持在2260米相同时间，但不使用L-精氨酸处理。用PowerLab系统测量平均肺动脉压。在显微镜下观察肺组织的形态和免疫组化变化。分别通过实时聚合酶链反应和蛋白质印迹法测量ODC1的mRNA和蛋白质水平。
低压缺氧导致暴露于6000米急性缺氧大鼠肺间质充血和毛细血管扩张。平均肺动脉压以及ODC1的mRNA和蛋白质水平显著升高，L-精氨酸处理可使其减弱。
L-精氨酸可减轻急性低压缺氧诱导的大鼠肺组织平均肺动脉压升高和ODC1基因表达增加。ODC1基因促成了缺氧性肺动脉高压的发展。
