低氧亲和力血红蛋白类氧载体的制备及大鼠动脉血压响应  

Preparation of Hemoglobin-based Oxygen Carrier with Low Oxygen Affinity and Arterial Blood Pressure Responses in Rat

作　　者：严坤平[1,2] 惠文利[1] 罗超 谢于斗 彭明丽[1,2] 陈超[1,3] 

机构地区：[1]西北大学生命科学学院,西安710069 [2]陕西北美基因股份有限公司,西安710069 [3]国家微检测工程研究中心,西安710069

出　　处：《高等学校化学学报》2011年第4期897-902,共6页Chemical Journal of Chinese Universities

基　　金：国家"八六三"计划项目(批准号:2006AA02A143);陕西省教育厅专项科研计划项目(批准号:09JK784)资助

摘　　要：制备了两种低氧亲和力的血红蛋白氧载体.用高碘酸钠氧化棉籽糖(高碘酸钠/棉籽糖摩尔比6∶1),得到氧化均一的开环棉籽糖;以其作为交联剂聚合脱氧猪血红蛋白,聚合1 h时得到了低氧亲和力(p50=5.75 kPa)的主要为分子内交联的分子量为64000的血红蛋白;聚合24 h时得到了低氧亲和力(p50=6.87kPa)的平均分子量为600000的聚合血红蛋白.分别进行大鼠50%等容量换血实验,前者显著引起血压升高而后者血压平稳,证实高血压主要与分子量为64000的血红蛋白有关,低氧亲和力不是造成高血压的主要原因.Hemoglobin-based oxygen carriers（HBOCs） is a universally compatible,immediately available,oxygen-carrying resuscitative fluid being developed as a red cell substitute for use in urgent blood loss.The oxygen affinity is one of the most important parameters of HBOCs,and is not completely understood at present.It was reported that the low oxygen affinity is the main reason for vasoconstriction（hypertension） in transfusion.In order to study the relationship between the oxygen affinity and the hypertension,two different o-raffinose crosslinked hemoglobin-based oxygen carriers with low oxygen affinity,polymerized porcine hemoglobin（pPolyHb） and intra-molecular cross-linked porcine hemoglobin（pCLHb）,were prepared and used to compare their effect on blood pressure in rat.The raffinose was first oxidized by sodium periodate（sodium periodate∶raffinose=6∶1,molar ratio）,yielding a completely oxidized and homogeneous polyaldehyde ring-opened raffinose（o-raffinose）,the cross-linker for polymerizing porcine deoxyhemoglobin.A low oxygen affinity（p50=5.75 kPa） and mainly intra-molecular cross-linked 64000 hemoglobin（pCLHb） was produced when treated by o-raffinose for 1 h,and was further purified to yield a homogeneous 64000 pCLHb.When treated for 24 h,a high molecular weight（600000） with low oxygen affinity（p50=7.87 kPa） polymerized hemoglobin（pPolyHb） was produced.These two products were then used for 50% isovolemic exchange transfusion in rat.The results show that the pCLHb caused an immediate and sustained hypertension while the blood pressure of pPolyHb treated rat keeps normal,suggesting that hypertension was related to the 64000 hemoglobin and low oxygen affinity wasn＇t the main cause of hypertension.

关 键 词：猪血红蛋白 棉籽糖 血红蛋白氧载体 氧亲和力 高血压 

分 类 号：O631.5[理学—高分子化学]