聚乙二醇化牛血红蛋白作为有效的基于血红蛋白的氧气载体,Biotechnology Progress

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聚乙二醇化牛血红蛋白作为有效的基于血红蛋白的氧气载体
Biotechnology Progress ( IF 2.5 ) Pub Date : 2016-10-31 , DOI: 10.1002/btpr.2380
Ying Wang ₁ , Linli Wang _{1,

2} , Weili Yu ₃ , Dawei Gao ₂ , Guoxing You ₁ , Penglong Li ₁ , Shan Zhang _{1,

2} , Jun Zhang ₁ , Tao Hu ₃ , Lian Zhao ₁ , Hong Zhou ₁

Affiliation

基于血红蛋白（Hb）的氧气载体（HBOC）已在外科医学和缺血性卒中的氧气疗法中用作血液替代品。作为有效的HBOC，聚乙二醇化的血红蛋白因其氧气输送和血浆扩展能力而备受关注。已经使用人类成人血红蛋白（HbA）作为原始底物开发了两种PEG化Hb，Euro-Hb和MP4用于临床试验。但是，HbA是从过时的人血中获得的，从此来源可获得的量可能不足以大规模生产PEG化HbA。相反，牛Hb（bHb）的充足资源没有数量限制。因此，bHb有可能充当获得PEG化bHb（bHb-PEG）的替代底物。使用马来酰亚胺化学法在与HbA-PEG相同的反应条件下制备bHb-PEG。结构上确定了bHb-PEG的功能，溶液和生理特性，并将其与HbA-PEG的功能，溶液和生理特性进行了比较。bHb‐PEG显示出更高的流体力学体积，胶体渗透压，粘度和P比HbA‐PEG高₅₀倍。bHb的高P ₅₀可以部分补偿HbA从R到T状态转变中的聚乙二醇化诱导的扰动。bHb-PEG无血管活性，可有效恢复失血性休克小鼠的平均动脉压。因此，bHb-PEG因其高氧传递和强大的血浆扩展能力而有望作为有效的HBOC。©2016美国化学工程师学会生物技术。Prog。，33：252–260，2017

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A PEGylated bovine hemoglobin as a potent hemoglobin‐based oxygen carrier

Hemoglobin (Hb)‐based oxygen carriers (HBOCs) have been used as blood substitutes in surgery medicine and oxygen therapeutics for ischemic stroke. As a potent HBOC, the PEGylated Hb has received much attention for its oxygen delivery and plasma expanding ability. Two PEGylated Hbs, Euro‐Hb, and MP4 have been developed for clinical trials, using human adult hemoglobin (HbA) as the original substrate. However, HbA was obtained from outdated human blood and its quantity available from this source may not be sufficient for mass production of PEGylated HbA. In contrast, bovine Hb (bHb) has no quantity constraints for its ample resource. Thus, bHb is of potential to function as an alternative substrate to obtain a PEGylated bHb (bHb‐PEG). bHb‐PEG was prepared under the same reaction condition as HbA‐PEG, using maleimide chemistry. The structural, functional, solution and physiological properties of bHb‐PEG were determined and compared with those of HbA‐PEG. bHb‐PEG showed higher hydrodynamic volume, colloidal osmotic pressure, viscosity and P₅₀ than HbA‐PEG. The high P₅₀ of bHb can partially compensate the PEGylation‐induced perturbation in the R to T state transition of HbA. bHb‐PEG was non‐vasoactive and could efficiently recover the mean arterial pressure of mice suffering from hemorrhagic shock. Thus, bHb‐PEG is expected to function as a potent HBOC for its high oxygen delivery and strong plasma expanding ability. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:252–260, 2017

更新日期：2016-10-31

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