戊二醛与双阿司匹林双聚合红细胞代用品的制备和动物实验疗效初步观察  

Preparation of a novel double polymerized of red blood cell substitute and preliminary observation of its curative effect

作　　者：周文涛[1] 李燊[1] 郝莎莎[1] 张鸿辉[1] 刘嘉馨[1] 王红[1] 杨成民[1] ZHOU Wentao;LI Shen;HAO Shasha;ZHANG Honghui;LIU Jiaxin;WANG Hong;YANG Chengmin(Institute of Blood Transfusion,Chinese Academy of Medical Sciences and Peking Union Medical College,Chengdu,610052,China)

机构地区：[1]中国医学科学院北京协和医学院输血研究所,四川成都610052

出　　处：《中国输血杂志》2022年第8期805-810,共6页Chinese Journal of Blood Transfusion

基　　金：中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-060)。

摘　　要：目的制备采用戊二醛(GDA)和双阿司匹林(DBBF)双聚合红细胞代用品并评价其初步疗效。方法选取影响DBBF与人胎盘血红蛋白聚合的影响因素,包括溶液pH,肌醇六磷酸浓度以及DBBF与血红蛋白摩尔比,确定GDA与DBBF-Hb聚合中间产物的摩尔比,并研究其制备过程中P_(50)、希尔系数以及高铁血红蛋白(MetHb)含量变化,制品再通过超滤、过滤、脱氧等步骤得到终产品并进行抗失血性休克大鼠疗效研究。结果在溶液pH为8.0,肌醇六磷酸浓度为10mM/L,DBBF与血红蛋白摩尔比为6∶1条件下,二聚体含量(22.67±3.28)%,四聚体含量(74.64±7.05)%,其P_(50)为(25.25±2.31)mmHg,其P_(50)和MetHb含量会随着DBBF与血红蛋白摩尔比的提升而逐步提升,希尔系数会随着DBBF与血红蛋白摩尔比的提升而逐步降低。GDA与DBBF-Hb聚合中间产物的摩尔比为7∶1时,二聚体含量(8.23±0.79)%,四聚体含量(27.87±3.63)%,超大分子含量(1.05±0.31)%,其MetHb含量会随着GDA与DBBF-Hb摩尔比的提升而逐步提升,P_(50)值和希尔系数会随着GDA与DBBF-Hb摩尔比的提升而逐步降低。该制品对大失血性休克大鼠24h的存活率均为83.33%(10/12)明显高于阴性对照组41.67%(5/12),与阳性对照组91.67%(11/12)大鼠存活率差异无统计学意义。结论通过戊二醛和DBBF双聚合红细胞代用品可以有效的降低二聚体的含量,更利于产业化生产,对抗失血性休克治疗具有积极意义。Objective To study the red blood cell substitute preparation method of glutaraldehyde(GDA)and Bis(3,5-dibromosalicyl)fumarate(DBBF)double polymerized,and also observe its curative effect.Methods The affecting factors of the crosslink of DBBF and human placental hemoglobin(Hb)were selected,including solution pH,inositol hexaphosphoric acid concentration,and molar ratios of DBBF/Hb.The changes of P_(50),Hill Co and methemoglobin(MetHb)content during the preparation process were studied and the molar ratio of GDA to DBBF-Hb were determined.The final product was obtained through the steps of ultrafiltration,filtration,and deoxygenation,etc.,and the final product was subjected to a study on the curative effect of anti-hemorrhagic shock in rats.Results Under the condition of pH 8.0,the concentration of inositol hexaphosphoric acid was 10mM/L,the molar ratio of DBBF/hemoglobin was 6∶1,the content of dimer was(22.67±3.28)%,the content of tetramer was(74.64±7.05)%,and its P_(50) was(25.25±2.31)mmHg.As the molar ratio of DBBF/Hb increased,P_(50) and MetHb content would gradually increase,while the Hill Co will gradually decrease.The molar ratio of GDA and DBBF-Hb was 7∶1,the content of dimer was(8.23±0.79)%,the content of tetramer was(27.87±3.63)%,the content of super-macromolecule was(1.05±0.31)%.As the molar ratio of GDA and DBBF/Hb increased,MetHb content would increase,while the P_(50) and Hill Co would gradually decrease.The 24h survival rate of the product in rats with hemorrhagic shock was 83.33%(10/12),which was significantly higher than that in the negative control group[41.67%(5/12)],while similar with the positive control group[91.67%(11/12)].Conclusion The red blood cell substitutes with GDA and DBBF double polymerized can effectively reduce the dimer content,which is more conducive to industrial production,and has a positive effect on the treatment of hemorrhagic shock.

关 键 词：戊二醛 双阿司匹林 双聚合 红细胞代用品 P50 

分 类 号：R392-33[医药卫生—免疫学]