School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.
College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.
Zool Res. 2022 Jul 18;43(4):497-513. doi: 10.24272/j.issn.2095-8137.2022.011.
Oxygen is essential for most life forms. Insufficient oxygen supply can disrupt homeostasis and compromise survival, and hypoxia-induced cardiovascular failure is fatal in many animals, including humans. However, certain species have adapted and evolved to cope with hypoxic environments and are therefore good models for studying the regulatory mechanisms underlying responses to hypoxia. Here, we explored the physiological and molecular responses of the cardiovascular system in two closely related hypoxia-adapted species with different life histories, namely, Qinghai voles ( ) and Brandt's voles ( ), under hypoxic (10% O for 48 h) and normoxic (20.9% O for 48 h) exposure. Kunming mice ( ) were used for comparison. Qinghai voles live in plateau areas under hypoxic conditions, whereas Brandt's voles only experience periodic hypoxia. Histological and hematological analyses indicated a strong tolerance to hypoxia in both species, but significant cardiac tissue damage and increased blood circulation resistance in mice exposed to hypoxia. Comparative transcriptome analysis revealed enhanced oxygen transport efficiency as a coping mechanism against hypoxia in both and , but with some differences. Specifically, showed up-regulated expression of genes related to accelerated cardiac contraction and angiogenesis, whereas showed significant up-regulation of erythropoiesis-related genes. Synchronized up-regulation of hemoglobin synthesis-related genes was observed in both species. In addition, differences in cardiometabolic strategies against hypoxia were observed in the rodents. Notably, relied on adenosine triphosphate (ATP) generation via fatty acid oxidation, whereas shifted energy production to glucose oxidation under hypoxic conditions and employed a conservative strategy involving down-regulation of fatty acid and glucose oxidation and a bradycardia phenotype. In conclusion, the cardiovascular systems of and have evolved different adaptation strategies to enhance oxygen transport capacity and conserve energy under hypoxia. Our findings suggest that the coping mechanisms underlying hypoxia tolerance in these closely related species are context dependent.
氧气是大多数生命形式所必需的。氧气供应不足会破坏体内平衡并危及生存，而缺氧引起的心血管衰竭在许多动物（包括人类）中是致命的。然而，某些物种已经适应并进化以应对低氧环境，因此是研究缺氧反应调节机制的良好模型。在这里，我们研究了两种密切相关的适应低氧环境的物种（青海田鼠和布氏田鼠）心血管系统在低氧（10% O ，48 h）和常氧（20.9% O ，48 h）暴露下的生理和分子反应，并用昆明小鼠作为比较。青海田鼠生活在高原地区的低氧环境中，而布氏田鼠仅经历周期性缺氧。组织学和血液学分析表明，两种物种对低氧都有很强的耐受性，但暴露于低氧中的小鼠心脏组织损伤明显，血液循环阻力增加。比较转录组分析表明，两种物种都通过提高氧气运输效率来应对低氧，但存在一些差异。具体而言，青海田鼠表现出与加速心脏收缩和血管生成相关的基因表达上调，而布氏田鼠则表现出明显的与红细胞生成相关的基因表达上调。两种物种的血红蛋白合成相关基因都呈现同步上调。此外，在这些啮齿动物中观察到了针对低氧的不同心脏代谢策略。值得注意的是，青海田鼠依赖于脂肪酸氧化产生三磷酸腺苷（ATP），而布氏田鼠在低氧条件下将能量产生转移到葡萄糖氧化，而昆明小鼠则采用保守策略，包括下调脂肪酸和葡萄糖氧化以及表现出心动过缓表型。总之，青海田鼠和布氏田鼠的心血管系统已经进化出不同的适应策略，以在低氧环境下增强氧气运输能力并节约能量。我们的研究结果表明，这些密切相关的物种在应对低氧耐受方面的适应机制是依赖于具体环境的。
