Wang Yaping, Zhao Zhen, Zhu Zhiyong, Li Pingying, Li Xiaolin, Xue Xiaohong, Duo Jie, Ma Yingcai
Department of Digestion, Qinghai Provincial People's Hospital, Xining, Qinghai, 810007, China.
J Physiol Anthropol. 2018 Feb 17;37(1):5. doi: 10.1186/s40101-018-0165-y.
The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues.
Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α).
Increased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α.
Acute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.
高海拔地区急性缺氧对心脏和肺组织细胞端粒长度的影响尚不清楚。本研究旨在探讨大鼠心脏和肺组织细胞在急性暴露于严重缺氧条件下的端粒长度变化及其在缺氧诱导的心脏和肺组织损伤中的作用。
将40只6周龄雄性Wistar大鼠随机分为对照组（n = 10）和缺氧组（n = 30）。对照组大鼠饲养于海拔1500米处，而缺氧组大鼠在低压氧舱中暴露于海拔5000米的模拟缺氧环境中1、3和7天（n = 10）。收集每只大鼠的左心室和右中叶组织，用于测量端粒长度和活性氧（ROS）含量，以及端粒酶逆转录酶（TERT）、缺氧诱导因子1α（HIF-1α）和缺氧诱导因子1α（HIF-2α）的mRNA和蛋白水平。
缺氧暴露时间增加会损伤大鼠心脏和肺组织细胞，增加ROS产生和端粒长度。缺氧大鼠中TERT和HIF-1α的mRNA和蛋白水平显著更高，且随暴露时间延长而增加；HIF-2α的mRNA和蛋白水平仅在缺氧7天的大鼠中增加。TERT与端粒长度和HIF-1α水平呈正相关，但与HIF-2α无关。
急性暴露于严重缺氧会因ROS产生而导致心脏和肺组织损伤，但通过上调TERT和HIF-1α促进端粒长度和适应性反应，从而保护心脏和肺组织细胞免受致命损伤。
