广东药科大学学报2025，Vol.41Issue(5)：1-12,12.DOI:10.16809/j.cnki.2096-3653.2025060404
乙酰苯肼联合环磷酰胺建立不同程度再生障碍性贫血大鼠模型及特点分析
Establishment of rat models with varying degrees of aplastic anemia using acetylphenylhydrazine combined with cyclophosphamide and analysis of their characteristics
摘要
Abstract
Objective To systematically evaluate the applicability of different doses of acetylphenylhydrazine(APH)and cyclophosphamide(CTX)in simulating chronic mild,moderate to severe,and acute aplastic anemia(AA)in humans.Methods Male SD rats were randomly divided into normal group and model low-,medium-,and high-dose groups(20 mg/kg,30 mg/kg,and 40 mg/kg).The AA rat model was established.The general condition,peripheral blood picture,tissue morphology,organ index,and bone marrow nucleated cell number were dynamically observed.The histopathology of liver,spleen,lung,and bone marrow was observed by HE staining.The bone marrow microenvironment,including microvessel density(MVD),vascular endothelial growth factor(VEGF),and Notch-1 protein expression,was detected by immunohistochemistry.Results Compared with the normal group,the model group rats showed a tendency to lie in groups,curl up and squint their eyes,experience hair loss and rapid breathing.The levels of peripheral blood red blood cells(RBC),white blood cells(WBC),platelets(PLT),and hemoglobin(HGB)were significantly reduced(P<0.05).Splenomegaly and thymic atrophy were obvious(P<0.05).The pathological damage of the spleen and bone marrow tissues was severe,with a significant increase in bone marrow pathological damage scores,a significant decrease in hematopoietic tissue proliferation and bone marrow nucleated cell count(BMNC)(P<0.01).The MVD in bone marrow tissue was significantly reduced,and the expression levels of VEGF and Notch-1 protein were significantly decreased(P<0.01).The low-dose group of the model showed mild chronic AA characteristics,which is conducive to rapid efficacy evaluation.The pathological characteristics of the medium-dose group in the model were highly similar to clinical AA,making it suitable for drug research on chronic moderate to severe AA.The high-dose group of the model showed acute systemic diseases and lacked AA specificity.Conclusion The combination of low and medium doses of APH and CTX can be used for drug research in the treatment of chronic mild and moderate to severe AA,respectively.The high-dose model is not suitable for AA specific studies.This study can provide a reliable experimental animal model for the research and development of AA therapeutic drugs.关键词
再生障碍性贫血/乙酰苯肼/环磷酰胺/大鼠模型Key words
aplastic anemia/acetylphenylhydrazine/cyclophosphamide/rat model分类
医药卫生引用本文复制引用
黄欣汝,吴香慧,李蔚怡,王长福..乙酰苯肼联合环磷酰胺建立不同程度再生障碍性贫血大鼠模型及特点分析[J].广东药科大学学报,2025,41(5):1-12,12.基金项目
广东省中药饮片规范化炮制技术工程研究中心建设项目(2017110) （2017110）
