Criswell K A, Sulkanen A P, Hochbaum A F, Bleavins M R
Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research, Warner-Lambert Co., Ann Arbor, MI 48105, USA.
J Appl Toxicol. 2000 Jan-Feb;20(1):25-34. doi: 10.1002/(sici)1099-1263(200001/02)20:1<25::aid-jat624>3.0.co;2-7.
This study was conducted to characterize better the response of rats to blood loss and hemolysis and to incorporate automated methods into the routine evaluations of those responses. Serial phlebotomies of 1.5-2.0 ml of blood per day for 5 days, or intraperitoneal injection of 50 mg kg(-1) phenylhydrazine (PHZ) for 3 days, were used to cause anemia associated with blood loss or hemolysis, respectively. Maximum decreases in red blood counts were observed on Day 3 in PHZ-treated animals (68%) and Day 4 in blood-loss animals (35%). In the routine complete blood count (CBC), hemoglobin, hematocrit/hemoglobin ratio and erythrocyte indices could be used to discriminate between the two treatments. Free plasma hemoglobin in PHZ-treated animals resulted in marked elevations of mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) with a 2:1 hematocrit/hemoglobin ratio rather than the anticipated 3:1 ratio. Although both groups of animals had elevated white blood cell counts, PHZ-treated animals also had monocytosis and basophilia. Reticulocyte counts were more sensitive than erythropoietin (EPO) concentrations in predicting erythroid changes. Maximum mean reticulocyte values were ca. 24% in serially phlebotomized animals and >99% in PHZ-treated rats. Plasma EPO levels were 4-10-fold higher than EPO levels in urine, kidney or liver. Flow cytometric differentials of rat bone marrow using 2, 7-dichlorofluorescin successfully predicted erythroid hyperplasia in both experimental groups. Erythrocyte indices returned to normal within 14 days and the remaining CBC parameters were normal within 28 days for both treatment groups. Reticulocyte counts remained slightly elevated on Day 28, but were normal when assessed at Day 56 in blood-loss and PHZ-treated animals.
本研究旨在更好地表征大鼠对失血和溶血的反应，并将自动化方法纳入对这些反应的常规评估中。分别采用每天进行1.5 - 2.0 ml的连续放血，持续5天，或腹腔注射50 mg kg(-1)苯肼（PHZ），持续3天，来分别导致与失血或溶血相关的贫血。在PHZ处理的动物中，第3天观察到红细胞计数最大降幅（68%）；在失血动物中，第4天观察到最大降幅（35%）。在常规全血细胞计数（CBC）中，血红蛋白、血细胞比容/血红蛋白比值和红细胞指数可用于区分这两种处理方式。PHZ处理的动物中游离血浆血红蛋白导致平均红细胞血红蛋白（MCH）和平均红细胞血红蛋白浓度（MCHC）显著升高，血细胞比容/血红蛋白比值为2:1，而非预期的3:1比值。尽管两组动物的白细胞计数均升高，但PHZ处理的动物还出现单核细胞增多和嗜碱性粒细胞增多。网织红细胞计数在预测红细胞系变化方面比促红细胞生成素（EPO）浓度更敏感。连续放血动物的最大平均网织红细胞值约为24%，PHZ处理的大鼠中则>99%。血浆EPO水平比尿液、肾脏或肝脏中的EPO水平高4 - 10倍。使用2,7 - 二氯荧光素对大鼠骨髓进行流式细胞术鉴别成功预测了两个实验组中的红细胞增生。两个治疗组的红细胞指数在14天内恢复正常，其余CBC参数在28天内恢复正常。在第28天，网织红细胞计数仍略有升高，但在失血和PHZ处理的动物中，在第56天评估时已恢复正常。
