Pathological changes of reactive thrombocytosis induced by recombinant human thrombopoietin in mice

Zhai Hailong; Wang Yufang

doi:10.13406/j.cnki.cyxb.001018

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Pathological changes of reactive thrombocytosis induced by recombinant human thrombopoietin in mice

更新时间：2024-01-17

- Pathological changes of reactive thrombocytosis induced by recombinant human thrombopoietin in mice
- Journal of Chongqing Medical University Vol. 42, Issue 9, Pages: 1161-1166(2017)
- 作者机构：
  
  1. 湖北理工学院医学院
  2. 黄石市中心医院血液内科
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.001018
  CLC： R558.3
- Published：2017，
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Zhai Hailong, Wang Yufang. Pathological changes of reactive thrombocytosis induced by recombinant human thrombopoietin in mice. [J]. Journal of Chongqing Medical University 42(9):1161-1166(2017)
DOI：

Zhai Hailong, Wang Yufang. Pathological changes of reactive thrombocytosis induced by recombinant human thrombopoietin in mice. [J]. Journal of Chongqing Medical University 42(9):1161-1166(2017) DOI： 10.13406/j.cnki.cyxb.001018.

摘要

目的:为了研究重组人血小板生成素(rhTPO)诱导小鼠反应性血小板增多症的病理变化。方法:将48只4周龄SPF级BALB/c小鼠

随机分为rhTPO组和对照组

各24只。rhTPO组每只小鼠每日腹腔注射rhTPO 500μg/(kg·d)

0.3 ml/只

对照组每只小鼠每日腹腔注射生理盐水0.3 m L/只

连续注射10 d。实验第3、5、7和10天

取2组小鼠各6只拉颈处死

检测两组小鼠的外周血细胞数量、血小板(platelet

PLT)聚集实验(platelet aggregation test

PAgT)、血小板ATP释放试验、血浆D-二聚体(D-dimer)浓度测定、小鼠血栓表现的观察、骨髓活检、脾、肝系数及脾、肝病理检查。结果:rhTPO组PLT数量在第3天明显高于对照组(P<0.05)

在第5、7和10天明显高于对照组(P<0.01)。rhTPO组5 min内最大凝集率和血小板ATP释放量在3、5、7和10天与对照组均无统计学差异(P>0.05)。rhTPO组血浆D-dimer浓度在第3、5、7和10天明显逐渐升高(P<0.01)

在第3天明显高于对照组(P<0.05)

在第5、7和10天明显高于对照组(P<0.01)。2组小鼠均无血栓表现。rhTPO组在第3、5、7和10天巨核细胞大量增生

体积增大

且随时间日益明显。rhTPO组脾系数在第5、7天均明显高于对照组(P<0.05)

在第10 d明显高于对照组(P<0.01)

rhTPO组肝系数在第10天明显高于对照组(P<0.05)。rhTPO组脾脏巨核系和脾体积在第3天内不变

但脾脏巨核系在第5、7和10天逐渐增生

第10天尚可见红系增生

脾体积在第5、7和10天逐渐增大。肝脏在第10天可见红系、粒系和巨核系增生且体积增大。结论:rhTPO诱导小鼠反应性血小板增多症的病理变化:骨髓中巨核细胞大量增生

外周血PLT数量急剧升高

但生成的PLT功能正常

初期

脾、肝未发生病理变化

中后期可刺激脾、肝先后髓外造血

体积先后增大。中后期可刺激脾脏巨核系逐渐增生

后期尚可见红系增生

脾体积也逐渐增大。肝在后期且可见红系、粒系和巨核系三系增生且体积增大。

Abstract

Objective:To investigate the pathological changes of reactive thrombocytosis induced by recombinant human thrombopoietin（rhTPO）in mice. Methods:Forty-eight 4-week-old SPF BALB/c mice were randomly divided into rhTPO group and control group

24 in each group. Mice in rhTPO group has been intraperitoneally injected rhTPO 500 μg/（kg·d）

0.3 ml daily for 10 days

while those in control group received saline 0.3 m L. Six mice in each group were executed on day 3

10 respectively;peripheral blood cell count was measured;PLT aggregation test（PAgT）

PLT ATP release test

plasma D-dimer concentration detection were conducted;manifestations of thrombosis in mice were observed;bone marrow biopsy as well as coefficient of spleen and liver and pathological examination of spleen and liver were all performed. Results:PLT was significantly higher in rhTPO group than in control group on day 3（P<0.05）and was significantly higher in rhTPO group than in control group on day 5

7 and 10（P<0.01）. There was no difference in five-min maximum aggregation rates and PLT ATP released quantities on day 3

10 between rhTPO group and control group（P>0.05）. Plasma D-dimer in rhTPO group were significantly higher than that in control group on day 3（P<0.05）and was significantly higher in rhTPO group than in control group on day 5

10（P<0.01）. Manifestations of thrombosis were not observed in both groups. Bone marrow biopsy for rhTPO group on day 3

10 showed megakaryocytic hyperplasia

increased volume

which became increasingly obvious as time went by. Spleen coefficients in rhTPO group were significantly higher than those in control group on day 5

and was significantly higher in rhTPO group than in control group on day 10（P<0.01）. Hepatic coefficients in rhTPO group were significantly higher than those in control group on day 10（P<0.05）. Megakaryocytes in spleen and spleen volume in rhTPO group were unchanged within 3 days

but megakaryocytes in spleen gradually proliferated on day 5

10. Erythroid proliferation was found on day 10. At the same time

spleen volume gradually increased on day 5

10. Erythroid

myeloid

megakaryocytic hyperplasia and increased volume were found in liver on day 10. Conclusion:Pathological changes of reactive thrombocytosis induced by high dose rhTPO in BALB/c mice include bone marrow megakaryocytes proliferation

a sharp increase in the number of peripheral blood PLT with normal PLT production function

no pathological change in spleen and liver at initial stage

extramedullary hematopoiesis and increased volume in spleen and liver at middle and late stage

megakaryocytic proliferation in spleen at middle and late stage

erythroid hyperplasia in spleen at late stage as well as increased spleen volume

erythroid

myeloid

megakaryocytic hyperplasia and increased volume in liver at late stage.

关键词

重组人血小板生成素小鼠反应性血小板增多症

Keywords

recombinant human thrombopoietinmicereactive thrombocytosis

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