Tan Hongying, Bi Jiangjiang, Wang Yunzhen, Zhang Junfeng, Zuo Zhiyi
1Department of Anesthesiology, University of Virginia, Charlottesville, VA. 2Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China. 3Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China. 4Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 5Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Crit Care Med. 2015 Aug;43(8):e276-86. doi: 10.1097/CCM.0000000000001023.
Transfusing RBCs stored for longer than 14 days (old RBC) in humans is common. This transfusion can injure organs, such as lungs and kidneys. We determined whether transfusion with old RBC injured brain.
Prospective, controlled animal study.
University research laboratory.
Adult male Sprague-Dawley rats.
Six-month-old Sprague-Dawley rats lost 20% total blood volume and then received RBC prepared from equal volume of the lost blood. RBC was stored for 1 day (fresh RBC) or 7 days (old RBC, storage lesions similar to those of human RBC stored for 28 d). Some rats received IV cell-free hemoglobin. These rats were not subjected to hemorrhage and RBC transfusion.
Rats were subjected to Barnes maze and fear conditioning tests from 1 week after blood transfusion. Rats transfused with old RBC but not fresh RBC took a longer time to identify the target hole in the Barnes maze and had less context-related fear conditioning behavior than control rats. Old RBC significantly increased interleukin 6 and ionized calcium-binding adapter molecule 1 in the hippocampus at 24 hours after the transfusion. These effects were attenuated by sulforaphane and minocycline, an antibiotic with anti-inflammatory property. Old RBC solution had a higher concentration of cell-free hemoglobin. Sulforaphane increased haptoglobin, a chelator of cell-free hemoglobin. Rats that received cell-free hemoglobin had a pattern of neuroinflammation and impairment of learning and memory similar to that of rats that received old RBC.
These results provide initial evidence to suggest that transfusion of old RBC induces neuroinflammation and impairment of learning and memory. These effects may be mediated by cell-free hemoglobin.
在人类中输注储存超过14天的红细胞（老化红细胞）很常见。这种输血会损伤器官，如肺和肾。我们确定输注老化红细胞是否会损伤大脑。
前瞻性对照动物研究。
大学研究实验室。
成年雄性Sprague-Dawley大鼠。
6个月大的Sprague-Dawley大鼠失血20%总血容量，然后接受从等量失血量中制备的红细胞。红细胞储存1天（新鲜红细胞）或7天（老化红细胞，储存损伤类似于储存28天的人类红细胞）。一些大鼠接受静脉注射无细胞血红蛋白。这些大鼠未经历出血和红细胞输血。
输血后1周对大鼠进行巴恩斯迷宫和恐惧条件反射测试。输注老化红细胞而非新鲜红细胞的大鼠在巴恩斯迷宫中识别目标洞的时间更长，与对照大鼠相比，情境相关的恐惧条件反射行为更少。输注老化红细胞后24小时，海马体中的白细胞介素6和离子化钙结合衔接分子1显著增加。这些作用被萝卜硫素和米诺环素（一种具有抗炎特性的抗生素）减弱。老化红细胞溶液中无细胞血红蛋白浓度更高。萝卜硫素增加了触珠蛋白，一种无细胞血红蛋白的螯合剂。接受无细胞血红蛋白的大鼠的神经炎症模式以及学习和记忆受损情况与接受老化红细胞的大鼠相似。
这些结果提供了初步证据，表明输注老化红细胞会诱导神经炎症以及学习和记忆受损。这些作用可能由无细胞血红蛋白介导。
