Xie Ling, Zhang Xuze, Qi Delin, Guo Xinyi, Pang Bo, Du Yurong, Zou Xiaoyan, Guo Songchang, Zhao Xinquan
Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; Key Laboratory of Crop Molecular Breeding, Xining, Qinghai Province, China; University of Chinese Academy of Sciences, China.
Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China.
Nitric Oxide. 2014 Apr 30;38:38-44. doi: 10.1016/j.niox.2014.02.009. Epub 2014 Mar 12.
Nitric oxide (NO), a potent vasodilator, plays an important role in preventing hypoxia induced pulmonary hypertension. Endogenous NO is synthesized by nitric oxide synthases (NOSs) from l-arginine. In mammals, three different NOSs have been identified, including neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Plateau pika (Ochotona curzoniae) is a typical hypoxia tolerant mammal that lives at 3000-5000 m above sea level on the Qinghai-Tibet Plateau. The aim of this study was to investigate whether NOS expression and NO production are regulated by chronic hypoxia in plateau pika. Quantitative real-time PCR and western blot analyses were conducted to quantify relative abundances of iNOS and eNOS transcripts and proteins in the lung tissues of plateau pikas at different altitudes (4550, 3950 and 3200 m). Plasma NO metabolites, nitrite/nitrate (NO(x)⁻) levels were also examined by Ion chromatography to determine the correlation between NO production and altitude level. The results revealed that iNOS transcript levels were significantly lower in animals at high altitudes (decreased by 53% and 57% at altitude of 3950 and 4550 m compared with that at 3200 m). Similar trends in iNOS protein abundances were observed (26% and 41% at 3950 and 4550 m comparing with at 3200 m). There were no significant differences in eNOS mRNA and protein levels in the pika lungs among different altitudes. The plasma NO(x)⁻ levels of the plateau pikas at high altitudes significantly decreased (1.65±0.19 μg/mL at 3200 m to 0.44±0.03 μg/mL at 3950 m and 0.24±0.01 μg/mL at 4550 m). This is the first evidence describing the effects of chronic hypoxia on NOS expression and NO levels in the plateau pika in high altitude adaptation. We conclude that iNOS expression and NO production are suppressed at high altitudes, and the lower NO concentration at high altitudes may serve crucial roles for helping the plateau pika to survive at hypoxic environment.
一氧化氮（NO）是一种强效血管舒张剂，在预防缺氧诱导的肺动脉高压中发挥重要作用。内源性NO由一氧化氮合酶（NOSs）从L-精氨酸合成。在哺乳动物中，已鉴定出三种不同的NOSs，包括神经元型NOS（nNOS）、内皮型NOS（eNOS）和诱导型NOS（iNOS）。高原鼠兔（Ochotona curzoniae）是一种典型的耐缺氧哺乳动物，生活在青藏高原海拔3000 - 5000米的地区。本研究的目的是调查高原鼠兔中NOS表达和NO生成是否受慢性缺氧调节。进行了定量实时PCR和蛋白质印迹分析，以量化不同海拔高度（4550、3950和3200米）的高原鼠兔肺组织中iNOS和eNOS转录本及蛋白质的相对丰度。还通过离子色谱法检测了血浆NO代谢产物亚硝酸盐/硝酸盐（NO(x)⁻）水平，以确定NO生成与海拔高度之间的相关性。结果显示，高海拔地区动物的iNOS转录水平显著降低（海拔3950米和4550米时分别比3200米时降低了53%和57%）。在iNOS蛋白丰度方面也观察到类似趋势（3950米和4550米时分别比3200米时降低了26%和41%）。不同海拔高度的鼠兔肺组织中eNOS mRNA和蛋白水平无显著差异。高海拔地区高原鼠兔的血浆NO(x)⁻水平显著降低（3200米时为1.65±0.19μg/mL，3950米时为0.44±0.03μg/mL，4550米时为0.24±0.01μg/mL）。这是首次描述慢性缺氧对高原鼠兔在高海拔适应中NOS表达和NO水平影响的证据。我们得出结论，高海拔地区iNOS表达和NO生成受到抑制，高海拔地区较低的NO浓度可能对帮助高原鼠兔在缺氧环境中生存起关键作用。
