母亲子痫前期对早产儿巨核细胞生成和血小板稳态的影响

Impact of preeclampsia on megakaryocytopoesis and platelet homeostasis of preterm infants

目的研究母亲子痫前期对早产儿巨核细胞生成和血小板稳态的影响。方法研究收集了26个母亲子痫前期的早产儿的脐血和母亲没有子痫前期的早产儿的脐血,分为子痫前期组（PE组）和母亲无子痫前期组（对照组）。分别通过全血渗透方法和血浆凝结培养系统检测循环中巨核细胞数量和巨核祖细胞集落形成单位（CFU-MK）的水平,通过流式细胞仪检测血小板活化标志物CD62P、CD63,通过ELISA检测两组血浆中可溶性血管内皮生长因子受体1（sFlt1）和TPO的水平。结果与对照组比较,PE组早产儿外周血的血小板计数减少[157.9（44.6）vs 239.6（57.5）×10^9/L,P〈0.001];循环中MK减少[5.8（1.0）vs 7.7（0.9）/mL,P〈0.001],CFU-MK减少[14.1（2.1）vs 20.1（2.8）/L×10^5 cell,P〈0.001];CD62P的表达增加[15.5（2.3）vs 11.4（1.9）%血小板,P〈0.001],CD63的表达增加[12.3（2.4）vs 9.0（1.6）%血小板,P〈0.001];血浆中sFlt1的水平升高[130.1（8.0）vs 97.7（8.7）pg/mL,P〈0.001],TPO的水平也升高[129.5（17.8）vs 98.9（11.8）pg/mL,P〈0.001]。PE组中,sFlt1的水平与血小板计数、CFU-MK和循环中MK数目呈负相关,与CD62P、CD63的表达呈正相关;TPO与血小板计数、CFU-MK和循环中MK数目无明显相关性;对照组中,sFlt1和TPO与上述参数无相关性。结论 sFlt1对于母亲子痫前期的早产儿在巨核细胞生成和血小板稳态方面起了重要作用。其作用机制可能与巨核细胞结构受损和血小板活化有关。

Objective To investigate the impact of preeclampsia on megakaryocytopoesis and platelet homeostasis of preterms.Methods A perspective case control study was performed on 26 cord blood samples of preterm newborns from mothers with preeclampsia（PE Group） and 26 cases of preterms from mothers without preeclampsia（Control Group）.Circulating megakaryocyte count and megakaryocyte colony forming units（CFU-MK） were quantified by whole blood infiltration method and plasma clot culture system respectively.Platelet activation markers CD62 P,CD63 were estimated by flow cytometry.Immunosorbent assays（ELISA） were employed to estimate plasma levels of soluble fms-like tyrosine kinase 1（sFlt1） and thrombopoietin（TPO） of two groups.Results When compared to the controls,infants born to mothers with preeclampsia had significantly lower peripheral platelet count[PE vs controls：（157.9± 44.6）×10^9/L vs（239.6±57.5）×10^9/L,P〈0.001],circulating MK count[（5.8 ±1.0）/mL vs（7.7±0.9）/mL,P〈0.001]and CFU-MK[（14.1 ±2.1）/10^5 cells vs（20.1±2.8）/10^5 cells,P〈0.001];Greater expressions of CD62P[（15.5 ±2.3）%vs（11.4 ±1.9）%of platelets,P〈0.001]and CD63[（12.3 ± 2.4）%vs（9.0 ± 1.6）%of platelets,P〈0.001];Increased plasma Flt level[（130.1±8.0）pg/mL vs（97.7 ±8.7）pg/mL,P〈0.001]and TPO level[（129.5 ±17.8）pg/mL vs（98.9±11.8）pg/mL,P〈0.001].In PE group,sFlt instead of TPO showed a significantly negative relationship with platelet counts,CFU-MK and circulating MK count,a positive relationship with CD62P、CD63 expressions.In control group,both sFlt and TPO didn＇t show any relationship with these parameters.Conclusions sFlt played important role in megakaryocytopoesis and platelet homeostasis in preterm infants from mothers with preeclampsia.Impaired megakaryocyte formation and increased platelet may be the reasons.