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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.

我们合成了S-亚硝基化聚乙二醇结合血红蛋白衍生物（SNO-Hb），它能提供一氧化氮（NO）和输送氧，并发现这种衍生物对失血性休克有治疗作用。本研究采用盲肠结扎穿刺术（CLP），用18 G针结扎盲肠2次，制备脓毒症（腹膜炎）模型。对照组（n=7）、麻醉组（n =5）、开腹组（n=5）和CLP组（n=6）的体温分别为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 mmHg、129 ± 7 mmHg、105 ±6 mmHg，心率分别为515±7次/min、466±14 mmHg、508± 25 mmHg、400 ±35 mmHg，CO_2产生量（各处理后1-2小时）分别为2.25±0.15g/BW·kg·h、2.06 ± 0.12、2.06 ± 0.10、1.43 ± 0.18。CLP大鼠代谢率降低，处于低动力状态，而非高动力循环状态，我们采用改良的代谢笼产生CO2，成功地测定了脓毒症大鼠的稳态代谢率，并通过改变盲肠结扎穿孔的大小，建立了高动力循环状态大鼠模型。