The Anti-Hypoxia Protective Effect of WYY026B by Interacting with Hemoglobin in Red Blood Cells

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Abstract

Background Exposure to hypoxia may experience damage to the heart, brain, lungs and other organs due to the low inspired O2. The improvement of endurance of human in resisting hypoxia and reducing hypoxia‑induced organ damage is an urgent problem to be solved. WYY026B is a honokiol derivatives by structural modification, and exhibits very potent pharma‑ cological activities and medicinal properties in brain ischemia/reperfusion (I/R) injury. Methods We used hypoxia model cerebral I/R model to identify the anti-hypoxia effect of WYY026B. High performance liquid chromatograph and immunofluorescence assay were used to detect the relationship between WYY026B and Red blood cells (RBCs). Interaction between WYY026B and hemoglobin (Hb) were validated by surface plasmon resonance assay (SPR). Results We demonstrated that WYY026B increased arterial oxygen saturation (SaO2) and arterial partial pressure of oxygen un‑ der hypoxia stress to improve the hypoxia tolerance. Blood gas analysis showed that WYY026B significantly decreased cervical venous SaO2 and increased arteriovenous oxygen partial pressure difference in I/R model. Nissl´s staining in‑ dicated that WYY026B significantly reduced the degree of hypoxia in brain tissue. A series of tests in vitro revealed that WYY026B could combine with RBCs. SPR assays showed that WYY026B interacted with Hb. Conclusion Overall, WYY026B maybe a new drug to enhance the ability of Hb to carry oxygen and to protect brain from the hypoxia injury
WYY026B与红细胞血红蛋白相互作用的抗缺氧保护作用
暴露于低氧环境中可能会由于低氧吸入而对心脏、大脑、肺和其他器官造成损伤。提高人体抗缺氧耐力,减少缺氧引起的器官损伤是一个亟待解决的问题。WYY026B是一种经结构修饰的厚朴酚衍生物,在脑缺血再灌注(I/R)损伤中表现出非常强的药理活性和药用特性。方法采用缺氧模型脑I/R模型,验证WYY026B的抗缺氧作用。采用高效液相色谱法和免疫荧光法检测WYY026B与红细胞的关系。通过表面等离子体共振实验(SPR)验证WYY026B与血红蛋白(Hb)的相互作用。结果WYY026B可提高低氧应激下的动脉血氧饱和度(SaO2)和动脉血氧分压,提高小鼠的缺氧耐受性。血气分析显示,WYY026B显著降低I/R模型颈静脉SaO2,升高动静脉氧分压差。Nissl染色显示WYY026B显著降低脑组织缺氧程度。一系列体外实验表明WYY026B能与红细胞结合。SPR实验显示WYY026B与Hb相互作用。结论WYY026B可能是一种增强血红蛋白携氧能力,保护脑缺氧损伤的新药物
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