重组人γ-干扰素联合白消安诱导建立小鼠重型再生障碍性贫血模型

Establishment of a severe aplastic anemia mouse model by using recombinant human interferon-gamma plus busulfan

背景:建立理想的重型再生障碍性贫血动物模型对探究再生障碍性贫血发病机制及筛选有效防治药物尤为重要。目的:应用注射用重组人γ-干扰素联合白消安建立小鼠重型再生障碍性贫血模型。方法:选择健康雌性昆明小鼠60只,随机分为再生障碍性贫血造模组(n=50)和对照组(n=10)。再生障碍性贫血造模组予重组人γ-干扰素1×104 U/d腹腔注射,以白消安18 mg/(kg·d)灌胃,均连续用药7 d;对照组给予同等容量生理盐水灌胃及腹腔注射。比较两组间一般情况、体质量及血细胞计数,并观察再生障碍性贫血造模组小鼠骨髓细胞形态学及骨髓活组织病理学的变化。结果与结论:给药第7天时,再生障碍性贫血造模组小鼠体质量、白细胞、血红蛋白、血小板及网织红细胞计数均较对照组明显下降,差异有显著性意义(P<0.05);骨髓细胞形态学及骨髓活组织病理学检查显示再生障碍性贫血造模组小鼠骨髓增生极度减低,非造血细胞团相对易见,油滴明显增多,脂肪空泡明显。提示联合应用重组人γ-干扰素和白消安能成功建立小鼠再生障碍性贫血模型,该造模方法操作简便,费用低,稳定性好。

BACKGROUND：It is important to establish an ideal mouse model of severe aplastic anemia for investigating the mechanism and finding new therapies for aplastic anemia. OBJECTIVE：To establish a severe aplastic anemia mouse model by using recombinant human interferon-γand busulfan. METHODS：Sixty healthy Kunming female mice were randomly divided into two groups：model group （n=50） and control group （n=10）. The model group was given recombinant human interferon-γat a dose of 1×104 U/d by intraperitoneal injection and busulfan at a dose of 18 mg/（kg·d） through stomach feeding for 7 days. The same volume of physiological saline was given to control group. Multi-parameters, including general condition, body weight, blood cellcount, morphology and biopsy of bone marrow were analyzed in two groups. RESULTS AND CONCLUSION：At day 7 after treatment, the weight, white blood cellcount, hemoglobin, blood platelet, reticulocyte count in model group were significantly lower than control group （P〈0.05）. Bone marrow smears and biopsy of model group showed marked reduction of bone marrow proliferation and increases of percentages of non-hematopoietic cellclusters and adipose tissue. The oil drop and fat vacuole were apparently seen in the model group. Severe aplastic anemia mouse model can be established by using recombinant human interferon-γand busulfan successful y, which is economic, stable and easy to operate.