Effect of recombinant human thrombopoietin on immune thrombocytopenia in pregnancy in a murine model
Effect of recombinant human thrombopoietin on immune thrombocytopenia in pregnancy in a murine model
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重组人血小板生成素对妊娠期免疫性血小板减少症小鼠模型的影响
DOI：
10.1016/j.intimp.2018.12.032
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发表时间：
2019-02-01
影响因子：
5.6
通讯作者：
Hou, Ming
中科院分区：
文献类型：
--
作者：
Liu, Yang;Wang, Rui;Hou, Ming
原发性免疫性血小板减少症(ITP)是一种严重的内科疾病，有可能导致母婴死亡。皮质类固醇、静脉注射免疫球蛋白或两者都是妊娠期ITP的一线治疗方法，但如果患者没有反应，选择就有限了。重组人血小板生成素(RhTPO)治疗慢性ITP已被证明是有效和安全的。然而，rhTPO治疗妊娠期ITP的有效性和安全性仍需进一步探讨。在这里，我们建立了一种理想的模拟人妊娠期ITP的小鼠模型，并评价了重组人TPO治疗妊娠期ITP的有效性和安全性。模型小鼠分别皮下注射0、150、1500、15000U/kg重组人TPO，连续14d。在第7天、第10天和第14天，rhTPO治疗组的血小板计数显著增加。在第20天，一半的母鼠被处死。经rhTPO处理后，CD4(+)T细胞中Tregs的比例显著高于对照组。Rh TPO治疗组大鼠血浆转化生长因子-β1水平显著高于对照组。胎儿大体及内脏检查未见明显异常。剩下的一半母鼠和它们的幼崽被观察了至少三周，以评估生命体征。未发现异常体征。此外，我们还探讨了其潜在的机制。结果表明，Tregs对c-MPL呈阴性反应，rh TPO对Tregs无直接影响。此外，经LY2109761治疗的模型小鼠脾中CD4(+)T细胞的Treg频率在统计学上低于对照组。因此，rhTPO可能是治疗妊娠期ITP的一种安全有效的方法。
Primary immune thrombocytopenia (ITP) is a serious medical disorder that has the potential for maternal and fetal mortality. Corticosteroids, intravenous immunoglobulin, or both are the first-line treatments for ITP in pregnancy, but choices are limited if patients fail to respond. Recombinant human thrombopoietin (rhTPO) has been proved effective and safe in management of chronic ITP. However, the efficacy and safety of rhTPO for pregnant ITP patients still need to be explored. Here we developed an ideal murine model that simulated human ITP in pregnancy and evaluated the efficacy and safety of rhTPO in management of ITP in pregnancy. Model mice were subcutaneously administered with 0, 150, 1,500 and 15,000 U/kg rhTPO for 14 days. Significant higher platelet counts were noted in rhTPO-treated groups on Day 7, 10 and 14. On Day 20, half the maternal mice were sacrificed. Frequencies of Tregs in CD4(+) T cells in rhTPO-treated groups were statistically higher than control. Significant higher plasma levels of TGF-beta 1 were observed in rhTPO-treated groups than control. There was no significant abnormality in gross or visceral examination of fetuses. The remaining half maternal mice and their pups were observed for at least three weeks to assess vital signs. No abnormal signs were noted.Furthermore, we investigated the underlying mechanisms. Results showed that Tregs were negative for c-Mpl and rhTPO had no direct effect on Tregs. Additionally, the Treg frequency in splenic CD4(+) T cells in LY2109761-treated model mice was statistically lower than control. Thus, rhTPO may be a safe and effective option for treatment of pregnant ITP patients.