抗原模拟法构建的免疫性血小板减少症小鼠模型中巨核细胞形态学及超微结构的研究

Morphocytology and Ultrastructure of Megakaryocytes in Immune Thrombocytopenia Mouse Model Established by Antigenic Mimicry Stimulation

目的:采用抗原模拟法构建免疫性血小板减少症(immune thrombocytopenia,ITP)小鼠模型,并观察模型小鼠的骨髓巨核细胞形态学及超微结构特点。方法:实验组CBA/Ht小鼠通过腹腔注射Wistar大鼠血小板免疫,对照组CBA/Ht小鼠仅注射0.9%氯化钠溶液。动态监测两组小鼠血小板计数,并取骨髓组织分别行涂片检查及扫描电镜观察。结果:与对照组比较,实验组小鼠在接受大鼠血小板免疫后第2周起血小板数量开始降低(P<0.05),至第4周达到最低点(P<0.01)。免疫后第4周实验组小鼠骨髓涂片中巨核细胞显著增生,且以幼稚巨核细胞为主;电镜下常可见巨核细胞核分叶减少,分界膜系统扩张或数量减少,胞浆内因颗粒物质减少且缺乏细胞器而显得更加致密,胞浆内常可见较多空泡。结论:该模型可较好地模拟人类ITP的发病特点,在模型中观察到的巨核细胞的形态及超微结构的改变进一步揭示了巨核细胞存在的发育异常与ITP的发病有关系。

Objective：To establish a mouse model of immune thrombocytopenia（ITP）by antigenic mimicry stimulation,and to observe the morphocytology and ultrastructure of megakaryocytes in the bone marrow.Methods：CBA/Ht mice in experimental group were immunized by intraperitoneal injection of platelets isolated from Wistar rats,while CBA/Ht mice in control group were injected with 0.9 % NaCl solution.The platelet count was monitored weekly.Bone marrow smears were observed with light microscope and electron microscope.Results：Compared with the control group,the platelet count of experimental group decreased at the second week after first injection（P〈0.05）,and reached its lowest point（P〈0.01）at the fourth week.In the bone marrow smears of experimental group at the fourth week,significant proliferation of megakaryocytes was found,and most of them were immature megakaryocytes.Electron microscopy examination of megakaryocytes in the experimental group showed a series of ultrastructural features including lobulated nucleus reduction,more vacuolization in cytoplasm,reduced or distended demarcation membrane system（DMS）,more dense and enlarged peripheral margins in the cytoplasm due to the lack of organelles and particulate matters.Conclusions：The mouse model of ITP established in this study has the clinical characteristics of ITP in humans.The morphological and ultrastructural alterations observed in this model suggest that abnormalities of megakaryocytes may exist in the pathogenesis of ITP.