Tan Yingxia, Ji Shouping, Li Subo, Wang Jiexi, Jin Xiaopan, Zhang Yangpei
Department of Blood Biochemistry and Molecular Biology Laboratory, Institute of Transfusion Medicine, Beijing, China.
Transfusion. 2008 Sep;48(9):1954-8. doi: 10.1111/j.1537-2995.2008.01786.x. Epub 2008 Jun 2.
Membrane grafting of methoxypolyethylene glycol (mPEG) provides a unique strategy in preventing the immunologic recognition in blood transfusion. mPEG-modified red blood cells (mPEG-RBCs) have acceptable in vitro properties and provide a useful solution to problems with clinical blood matching. The aim of this study was to demonstrate the physiologic normality of mPEG-RBCs in mice.
Mouse RBCs were withdrawn via cardiac bleed and modified with 1.0 mmol per L mPEG with succinimidyl propionate linker. The fluorescein-labeled mPEG-RBCs were then transfused into recipient mice for in vivo survival analysis. At the same time, the exsanguine mouse model was produced, and mice were transfused with mPEG-RBCs. The effects of mPEG-RBC transfusion on the hemoglobin (Hb) level, swimming endurance capacity, and hypoxic-ischemic injury in hippocampal pyramidal cells of exsanguine mice were investigated.
mPEG-RBCs showed the same in vivo survival curve and t((1/2)) as those of untreated RBCs. Transfusion of mPEG-RBCs could elevate Hb level of exsanguine mice and improve their swimming endurance capacity, and histologic studies showed that mPEG-RBCs could also restore the hypoxic-ischemic injury of hippocampal pyramidal cells in exsanguine mice, which were similar with control RBCs. That is, mPEG-RBCs functioned in a similar fashion to untreated RBCs in exsanguine mice. Therefore, these results revealed that mPEG-RBCs had normal oxygen-carrying capacity.
In conclusion, the results confirmed that mPEG-RBCs could perform their in vivo function of carrying O(2) and improve some physiologic indexes of exsanguine mice, and the physiologic normality of mPEG-RBCs provides new findings for clinical use.
甲氧基聚乙二醇(mPEG)膜接枝为预防输血中的免疫识别提供了一种独特策略。mPEG修饰的红细胞(mPEG-RBCs)具有可接受的体外特性,并为临床血液配型问题提供了有用的解决方案。本研究的目的是证明mPEG-RBCs在小鼠体内的生理正常性。
通过心脏采血获取小鼠红细胞,并用含琥珀酰亚胺丙酸酯连接子的1.0 mmol/L mPEG进行修饰。然后将荧光素标记的mPEG-RBCs输注到受体小鼠体内进行体内存活分析。同时,建立放血小鼠模型,并给小鼠输注mPEG-RBCs。研究了mPEG-RBCs输血对放血小鼠血红蛋白(Hb)水平、游泳耐力以及海马锥体细胞缺氧缺血性损伤的影响。
mPEG-RBCs显示出与未处理红细胞相同的体内存活曲线和半衰期(t(1/2))。输注mPEG-RBCs可提高放血小鼠的Hb水平并改善其游泳耐力,组织学研究表明mPEG-RBCs还可恢复放血小鼠海马锥体细胞的缺氧缺血性损伤,这与对照红细胞相似。也就是说,在放血小鼠中,mPEG-RBCs的功能与未处理的红细胞相似。因此,这些结果表明mPEG-RBCs具有正常的携氧能力。
总之,结果证实mPEG-RBCs能够发挥其在体内携带O₂的功能,并改善放血小鼠的一些生理指标,mPEG-RBCs的生理正常性为临床应用提供了新的发现。