1Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan, China.2Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Crit Care Med. 2016 Nov;44(11):e1090-e1096. doi: 10.1097/CCM.0000000000001825.
To evaluate the resuscitative efficacy and the effect on reperfusion injury of two site-specific PEGylated human serum albumins modified with linear or branched PEG20kDa, compared with saline, 8% human serum albumin and 25% human serum albumin, in a hemorrhagic shock model.
Laboratory.
Male Wistar rats.
Prospective study.
Rats were bled to hemorrhagic hypovolemic shock and resuscitated with different resuscitation fluids.
The mean arterial pressure and blood gas variables were measured. Hemorheology analysis was performed to evaluate the influence of resuscitation on RBCs and blood viscosity. The microvascular state was indirectly characterized in terms of monocyte chemotactic protein-1 and endothelial nitric oxide synthase that related to shear stress and vasodilation, respectively. The levels of inflammation-related factors and apoptosis-related proteins were used to evaluate the reperfusion injury in lungs. The results showed that PEGylated human serum albumin could improve the level of mean arterial pressure and blood gas variables more effectively at the end of resuscitation. poly(ethylene glycol) modification was able to increase the viscosity of human serum albumin to the level of effectively enhancing the expression of monocyte chemotactic protein-1 and endothelial nitric oxide synthase, which could promote microvascular perfusion. The hyperosmotic resuscitative agents including both 25% human serum albumin and PEGylated human serum albumins could greatly attenuate lung injury. No significant therapeutic advantages but some disadvantages were found for Y shaped poly(ethylene glycol) modification over linear poly(ethylene glycol) modification, such as causing the decrease of erythrocyte deformability.
Linear high molecular weight site-specific PEGylated human serum albumin is recommended to be used as a hyperosmotic resuscitative agent.
评估两种特定部位聚乙二醇化人血清白蛋白（分别用线性或支链聚乙二醇 20kDa 修饰）相对于生理盐水、8%人血清白蛋白和 25%人血清白蛋白的复苏效果及其对再灌注损伤的影响，在失血性休克模型中。
实验室。
雄性 Wistar 大鼠。
前瞻性研究。
大鼠失血性低血容量性休克并接受不同复苏液复苏。
测量平均动脉压和血气变量。进行血液流变学分析，评估复苏对 RBC 和血液粘度的影响。间接用单核细胞趋化蛋白-1 和内皮型一氧化氮合酶来描述微血管状态，分别与切应力和血管扩张有关。炎症相关因子和凋亡相关蛋白的水平用于评估肺再灌注损伤。结果表明，聚乙二醇化人血清白蛋白在复苏结束时能更有效地提高平均动脉压和血气变量水平。聚乙二醇修饰能够增加人血清白蛋白的粘度，达到有效增强单核细胞趋化蛋白-1 和内皮型一氧化氮合酶表达的水平，从而促进微血管灌注。高渗复苏剂包括 25%人血清白蛋白和聚乙二醇化人血清白蛋白都能显著减轻肺损伤。Y 型聚乙二醇修饰相对于线性聚乙二醇修饰并没有明显的治疗优势，但也有一些缺点，如红细胞变形性下降。
推荐使用线性高分子量特异性聚乙二醇化人血清白蛋白作为高渗复苏剂。
