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正常及甲氧基聚乙二醇修饰的小鼠红细胞对缺氧小鼠游泳耐力和海马损伤的比较评估

Comparative assessment of normal and methoxypolyethylene glycol-modified murine red cells on swimming endurance and hippocampal injury in hypoxic mice.

作者信息

Tan Yingxia, Ji Shouping, Li Subo, Wang Jiexi, Jin Xiaopan, Zhang Yangpei

机构信息

Department of Blood Biochemistry and Molecular Biology Laboratory, Institute of Transfusion Medicine, Beijing, China.

出版信息

Transfusion. 2008 Sep;48(9):1954-8. doi: 10.1111/j.1537-2995.2008.01786.x. Epub 2008 Jun 2.

Abstract

BACKGROUND

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.

STUDY DESIGN AND METHODS

Mouse RBCs were withdrawn via cardiac bleed and modified with 1.0 mmol per L mPEG with succinimidyl propionate linker.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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

研究设计与方法

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。

结果

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。

结论

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。

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