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

我们研制了一种既能供氧又能供氧的S-亚硝基聚乙二醇偶联型血红蛋白衍生物(SNO-Hb)，对大鼠失血性休克有一定的治疗作用。在这项研究中，我们将使新的血红蛋白衍生物用于存在大量NO和周围组织氧摄取受损的脓毒症。用250~300g体重的Spraugue-Dowley大鼠3进行盲肠结扎穿刺术(CLP，结扎的盲肠用18G针穿两次)，制作脓毒症模型(腹膜炎)。对照组(n=7)、麻醉组(n=5)、剖腹组(n=5)、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、120±4、129±7、105±6，心率分别为515±7/min、466±14、508±25、400±35，二氧化碳产生量(各处理后1~2小时)分别为2.25±0.15、2.06±0.12、2.06±0.10、1.43±0.18。在CLP大鼠，代谢率下降，不是处于高动力循环状态，而是处于低动力状态。我们成功地测定了脓毒症大鼠稳定的代谢率，通过改变结扎盲肠穿刺孔的大小来制作高动力循环状态大鼠模型。

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.