在心血管和代谢功能障碍的非肥胖模型中的新型高分子量聚合血红蛋白
Cynthia R Muller1, Alexander T Williams1, Allyn M Eaker1
1Department of Bioengineering, University of California, San Diego, CA, USA.
概括
高热量饮食会导致代谢障碍,在创伤期间增加风险. 基于血红蛋白的氧载体 (HBOC),如PolyHb,作为血液的替代品进行了测试. 新的 PolyhHb 显示的心脏毒性比较小,即使在不健康的模型中,也比较少.
科学领域:
- 生物医学工程 生物医学工程
- 毒理学 毒理学 毒理学
- 心血管研究研究心血管研究
背景情况:
- 高卡路里,高脂肪,高糖饮食 (HFHSD) 导致代谢障碍和心血管疾病.
- 代谢障碍增加了感染和创伤严重后果的易感性,突出了血液替代品的需要.
- 高分子量聚合人体血红蛋白 (PolyhHb) 是一种潜在的红细胞 (RBC) 替代品.
研究的目的:
- 评估PolyHb和Oxyglobin (低MW聚合牛血红蛋白) 输血在饮食引起的代谢障碍的几内亚猪中的毒性.
- 评估先前存在的代谢条件对基于血红蛋白的氧载体 (HBOCs) 安全性的影响.
主要方法:
- 几内亚猪被养HFHSD12周以诱导代谢障碍.
- 使用PolyHb或Oxyglobin进行了20%的血液体积交换输血.
- 输血后评估了肝损伤和心脏功能障碍标志物.
主要成果:
- 两种PolyhHb和Oxyglobin输血都导致肝损伤,HFHSD养动物的肝损伤更严重.
- 氧化球蛋白输血导致HFHSD和正常饮食组的心脏功能障碍.
- 高MW PolyhHb与低MW Oxyglobin相比显示出较低的心脏毒性,即使在代谢挑战的动物中也是如此.
结论:
- 预先存在的代谢障碍可能会加剧与HBOC相关的副作用.
- 较新的高MW PolyhHb在心脏毒性方面比较安全,而不是较旧的低MW Oxyglobin.
- 高MW PolyhHb代表了对输血医学的HBOC开发的有希望的进步,特别是在弱势群体.
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