背景：聚合人脐带血红蛋白（polymerized human cord hemoglobin PolyCHb）是血红蛋白类氧载体（hemoglobin -based oxygen carriers，HBOCs）的一种，其在休克及换血模型中，可提高动物存活率，改善微循环，并在休克早期为缺血组织器官供氧，减轻缺血缺氧造成的损伤。在过去的HBOCs临床研究中发现，输注HBOCs可造成血管活性改变、心脏损伤、肾毒性等不良反应，本课题将根据前期实验室研究结果，选用800 mg/kg PolyCHb直接输注，初步探讨其对大鼠心肌组织及内皮细胞的影响，同时选用不同干预方式，探讨其对大鼠心功能的影响。

目的：本课题选用大鼠直接输注聚合人脐带血红蛋白，初步研究其对心肌组织的影响。

方法：将SD大鼠随机分为假手术组（sham组）、生理盐水组（NaCl组）和PolyCHb （800 mg/kg）组，直接输注对应溶液，记录并检测基础值、输注后0min、10min、20min、30min、60min大鼠平均动脉压（MAP）、心率（HR）、及大鼠心功能指标（左心室收缩末压pes、左心室舒张末压ped、dp/dt max、dp/dt min、等容舒张时间常数Tau、心输出量CO）的值，并计算总外周血管阻力（TPVR）的变化值。另取SD大鼠，分组同上，在输注后1h、3h、6h，取血浆测定肌酸激酶同工酶（CK-MB）、肌钙蛋白（cTnI）含量，在输注溶液后6h，将大鼠处死，取心脏组织，用4%多聚甲醛固定，进行病理切片及免疫组化（CK-MB、cTnI、S100A1、心型脂肪酸结合蛋白H-FABP）的检测。取输注后1h、3h、6h血浆测定一氧化氮（NO）含量及内皮细胞损伤标志物内皮素-1（ET-1）、血管性假性血友病因子（vWF）、可溶性细胞间粘附分子-1（sICAM-1）。再取SD大鼠，分为三组，800mg/kg PolyCHb组、降低PolyCHb输注剂量（200 mg/kg PolyCHb组）及使用NO供体硝普钠（SNP）与800mg/kg PolyCHb联合输注（SNP+800mg/kg PolyCHb组），观察对心功能指标的影响。

结果：sham组与NaCl组心功能各指标无差异，输注PolyCHb后，血压及总外周血管阻力升高，心率及心输出量下降，后缓慢恢复，dp/dt max及dp/dt min值先略为下降后缓慢回升，Tau值升高。PolyCHb组输注后6h内血浆CK-MB及cTnI值先升高后降低，含量高于另外两组。输注后6h免疫组化及病理检测结果显示无损伤。血浆NO水平降低，输注后3h及6h与另外两组有统计学差异，内皮细胞损伤标志物各组之间无差异。PolyCHb（200mg/kg）组及使用SNP+800 mg/kg PolyCHb血压升高的幅度、Tau升高幅度、心率及心输出量降低的幅度比PolyCHb（800mg/kg）组低，dp/dt max及dp/dt min的变化也略有不同。

结论：输注800mg/kg PolyCHb后60min内，大鼠血压升高，心率及心输出量下降，心肌功能受到影响；在输注后6h未见病理损伤；输注后，血浆NO含量下降，但未造成造成内皮损伤；降低剂量（200mg/kg）及提供NO供体都可改善对单独给予PolyCHb的大鼠心肌功能的影响。

background: polymerized human cord hemoglobin (polychb) is a kind of hemoglobin-based oxygen carriers (hbocs), which can improve animal survival rate, microcirculation achieve oxygen supplement in the early stage and reduce the damage caused by ischemia and hypoxia. in the past clinical studies of hbocs, it was found that infusion of hbocs can cause side effects such as vasoactivity , cardiac involvement , renal toxicity, etc. according to the results of previous laboratory research, this study selected the dosage 800 mg/kg polychb for direct infusion to investigate its effects on myocardial tissue and endothelial cells in rats. at the same time, different intervention methods were used to explore their effects on cardiac function in rats.

ive: in this study,sd rats were directly infused with polymerized human cord hemoglobin to study its effects on myocardial tissue.

methods: sd rats were randomly divided into sham surgery group (sham group), saline group (nacl group) and polychb (800 mg/kg) group.animals in each group was infused with the corresponding solution. the baseline values of mean arterial pressure (map), heart rate (hr), and cardiac function in rats (left ventricular end-systolic pressure, left ventricular end-diastolic pressure, dp/dt max, dp/dt min, isovolumic relaxation time constant, cardiac output ) were recorded and detected at the time point of 0 min, 10 min, 20 min, 30 min, and 60 min after infusion, the values of total peripheral vascular resistance (tpvr) were calculated. another sd rats were randomly divided into three groups as above. at 1h, 3h, and 6h after infusion, creatine kinase isoenzyme (ck-mb) and troponin (ctni) in plasma were measured. at 6h after infusion, the rats were then sacrificed and the heart was taken and fixed with 4% paraformaldehyde for pathological section and immunohistochemistry detection (ck-mb, ctni, s100a1, heart-type fatty acid binding protein h-fabp). the contents of nitric oxide (no) and endothelial cell injury markers endothelin-1 (et-1), von willebrand factor (vwf), soluble intercellular adhesion molecule-1 (sicam-1) in plasma were measured at 1h, 3h, and 6h after infusion. additionally  rats were also divided into three groups, 800 mg/kg polychb group, reduced polychb infusion dose (200 mg/kg polychb) group, combined infusion with sodium nitroprusside (snp, an no donor) and 800 mg/kg polychb (snp +800mg/kg polychb group), observed the effects on cardiac function indicators.

results: there was no difference in cardiac function between sham group and nacl group. after infusion of polychb, blood pressure and total peripheral vascular resistance increased, heart rate and cardiac output decreased, and then slowly recovered. dp/dt max and dp/dt min slightly decreased, it slowly rised and the tau value rised. ck-mb and ctni values in plasma ​​increased and then decreased within 6 h after infusion in the polychb group, and the concentration in plasma were higher than the other two groups. immunohistochemistry and pathological examination at 6 h after infusion showed no damage. no in plasma decreased, the contents were lower than the other two groups at 3h and 6h after infusion. there was no difference in the endothelial cell injury markers among the three groups. the amplitude of the increase was observed in blood pressure, and tau, the decrease of heart rate and cardiac output in the polychb (200 mg/kg) group and the snp + 800 mg/kg polychb group were lower than those in the polychb (800 mg/kg) group, and the changes in dp/dt max and dp/dt min were slightly different.

conclusions: within 60 min after infusion of polychb, the blood pressure of rats increased, heart rate and cardiac output decreased, and myocardial function was affected. no pathological damage was observed at 6 h after infusion. no content in plasma was decreased ,and there was no endothelial injury, 200 mg/kg polychb group and snp + 800 mg/kg polychb group were all improved the effects of myocardial function in rats compared with given polychb alone.