In vivo blood flow abnormalities in the transgenic knockout sickle cell mouse
In vivo blood flow abnormalities in the transgenic knockout sickle cell mouse
复制标题
DOI：
10.1172/jci5977
复制
发表时间：
1999-03-01
影响因子：
15.9
通讯作者：
Cheung, ATW
中科院分区：
文献类型：
--
作者：
Embury, SH;Mohandas, N;Cheung, ATW
循环障碍对镰状细胞性贫血的公认重要性仍有待于体内实验的验证。活体显微镜研究的血流在病人中是有限的循环，可以看到非侵入性和限制故意扰动的循环。镰状血流异常的进一步知识还有待于人类镰状细胞病的动物模型。我们比较了正常小鼠和转基因敲除镰状细胞小鼠的粘膜肠微血管中的血流，所述转基因敲除镰状细胞小鼠具有仅含有人血红蛋白S的红细胞，并且表现出一定程度的溶血性贫血和类似于人类疾病的病理并发症。在镰状细胞小鼠中，除了看到血流异常，如所有微血管中的淤积，我们还检测到所有直径的小静脉中的血流速度降低。正常和镰状细胞小鼠对高氧的血流反应是戏剧性的，但相反：高氧迅速减缓或停止正常小鼠的血流，但明显增强镰状细胞小鼠的血流。活体显微镜下的研究，这种小鼠模型提供了重要的见解镰状细胞血流异常，并建议该模型可用于评估异常流量的原因和新的方法来治疗镰状细胞病。
The accepted importance of circulatory impairment to sickle cell anemia remains to be verified by in vivo experimentation. Intravital microscopy studies of blood flow in patients are limited to circulations that can be viewed noninvasively and are restricted from deliberate perturbations of the circulation. Further knowledge of sickle blood flow abnormalities has awaited an animal model of human sickle cell disease. We compared blood flow in the mucosal-intestinal microvessels of normal mice with that in transgenic knockout sickle cell mice that have erythrocytes containing only human hemoglobin S and that exhibit a degree of hemolytic anemia and pathological complications similar to the human disease. In sickle cell mice, in addition to seeing blood flow abnormalities such as sludging in all microvessels, we detected decreased blood flow velocity in venules of all diameters. Flow responses to hyperoxia in both normal and sickle cell mice were dramatic, but opposite: Hyperoxia promptly slowed or halted flow in normal mice but markedly enhanced flow in sickle cell mice. Intravital microscopic studies of this murine model provide important insights into sickle cell blood flow abnormalities and suggest that this model can be used to evaluate the causes of abnormal flow and new approaches to therapy of sickle cell disease.