Department of Obstetrics and Gynecology, the Fifth People's Hospital of Jinan, Jinan, Shandong, China.
Department of Intensive Care Unit, the Fourth People's Hospital of Jinan, Jinan, Shandong, China.
J Mol Endocrinol. 2021 Mar;66(3):233-243. doi: 10.1530/JME-20-0308.
Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a life-threatening pregnancy complication. Though there are several medications widely used to treat HELLP syndrome, delivery is the only efficient treatment. The goal of the present study was to investigate the effects of platelet-derived growth factor-D (PDGF-D), a newly identified PDGF, in a rat model of HELLP syndrome which was accomplished by sFlt-1 and sEng injection. The expression levels of PDGF-D in pregnant women diagnosed with HELLP syndrome was determined. A HELLP rat model was established and the PDGF-D expression level in the plasma and the placenta tissue was evaluated. To evaluate the effects of PDGF-D in HELLP syndrome model, siPDGF-D was injected into the rats and the HELLP syndrome-related parameters were measured. The levels of inflammatory cytokines and PDGF-D were determined by ELISA. The oxidative stress activities in the plasma were also determined. Furthermore, the expression of PDGF-D/PDGFR-β/nuclear factor κB (NF-κB) p65 in placenta tissues was evaluated by Western blotting. Compared to the normal pregnant (NP) group, the levels of PDGF-D were augmented regardless of species. Knockdown of PDGF-D can result in the alleviation of HELLP syndrome development and progression in the HELLP rat model. Importantly, as a result of PDGF-D knockdown, the serum levels of inflammatory cytokines and oxidative stress activities were modulated, and the phosphorylation of PDGFR-β and NF-κB p65 in placenta tissue was inhibited. Taking together, our findings indicate that targeting PDGF-D could be used as a novel strategy to treat patients with HELLP syndrome.
溶血、肝酶升高和血小板减少症（HELLP）综合征是一种危及生命的妊娠并发症。尽管有几种药物广泛用于治疗 HELLP 综合征，但分娩是唯一有效的治疗方法。本研究的目的是通过 sFlt-1 和 sEng 注射研究新发现的血小板衍生生长因子-D（PDGF-D）在 HELLP 综合征大鼠模型中的作用。测定了诊断为 HELLP 综合征的孕妇中 PDGF-D 的表达水平。建立了 HELLP 大鼠模型，并评估了血浆和胎盘组织中 PDGF-D 的表达水平。为了评估 PDGF-D 在 HELLP 综合征模型中的作用，向大鼠注射 siPDGF-D，并测量 HELLP 综合征相关参数。通过 ELISA 测定炎性细胞因子和 PDGF-D 的水平。还测定了血浆中的氧化应激活性。此外，通过 Western blot 评估胎盘组织中 PDGF-D/PDGFR-β/核因子 κB（NF-κB）p65 的表达。与正常妊娠（NP）组相比，无论物种如何，PDGF-D 的水平均升高。敲低 PDGF-D 可导致 HELLP 大鼠模型中 HELLP 综合征的发展和进展得到缓解。重要的是，由于 PDGF-D 敲低，血清中炎性细胞因子和氧化应激活性的水平得到调节，胎盘组织中 PDGFR-β 和 NF-κB p65 的磷酸化受到抑制。综上所述，我们的研究结果表明，靶向 PDGF-D 可能是治疗 HELLP 综合征患者的一种新策略。
