New hemoglobin derivative aimed for improvement of oxygen metabolism in severe sepsis

新的血红蛋白衍生物旨在改善严重脓毒症的氧代谢

基本信息

批准号：
14370347
负责人：
SHINOZAWA Yotaro
金额：
$ 4.42万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370347/
关键词：
hemoglobin derivative sepsis CLP peritonitis metabolic rate CO2 production nitric oxide hyperdynamic state 敗血症循環動態

项目摘要

We have made S-Nitrosylated Polyethylene Glycol-conjugated Hemoglobin Derivative (SNO-Hb) which can donate nitric oxide (NO) as well as deliver the oxygen and have found this derivative is useful for the treatment of hemorrhagic shock in rat model. In this study, we are going to make new hemoglobin derivatiye useful in sepsis where plenty of NO exists and impaires oxygen uptake in the peripheral tissue.Cecum ligation puncture (CLP, ligated coecum was puctured twice by 18G needle) was performed in 250〜300g weighed Spraugue-Dowley rats3, making sepsis model (peritonitis). In control rats (n=7),anesthesia only (n=5),laparotomy only (n=5),and CLP (n=6),body temparature was 37.4±0.2℃,36.3±0.5,36.7±0.8,33.6±1.1,respectively, Also, blood pressure was 128±4 mmHg,120±4,129±7,105±6,respectively, heart rate was 515±7/min,466±14, 508±25,400±35,respectively, and CO2 production (1-2 hours post each procesure) was 2.25±0.15g/BWkg/hour, 2.06±00.12,2.06±0.10,1.43±0.18,respectiveiy. In CLP rats, metabolic rate was decreased and not in hyperdymanic circulatory state but in hypodymanic state.We could successfully measured stable metabolic rate in septic rats by the modified metabolic cage for CO2 production.We are going to make hyperdymanic circulatory state rat model by changing the size of puncture hole smaller in the ligated coecum.

我们制备了 S-亚硝基化聚乙二醇结合血红蛋白衍生物 (SNO-Hb)，它可以提供一氧化氮 (NO) 并输送氧气，并发现这种衍生物可用于治疗大鼠模型的失血性休克。研究中，我们将制造新的血红蛋白衍生物，用于治疗脓毒症，脓毒症中存在大量一氧化氮，会损害周围组织的摄氧量。盲肠结扎穿刺对250-300g体重的Sprague-Dowley大鼠进行CLP（CLP，用18G针穿刺两次结扎盲肠），制作败血症模型（腹膜炎）。对照大鼠（n=7），仅麻醉（n=5），仅剖腹探查。 (n=5) 和 CLP (n=6)，体温为分别为37.4±0.2℃、36.3±0.5、36.7±0.8、33.6±1.1，血压分别为128±4 mmHg、120±4、129±7、105±6，心率为515±7/min、466± 14, 分别为 508±25,400±35，以及CLP 大鼠的 CO2 产生量（每次手术后 1-2 小时）分别为 2.25±0.15g/BWkg/小时、2.06±00.12、2.06±0.10、1.43±0.18。通过改进的代谢笼成功测量了脓毒症大鼠的稳定代谢率CO2的产生。我们将通过改变结扎盲肠中穿刺孔的尺寸来制作高动力循环状态大鼠模型。