Chen Q, Zhao M, Guo F, Yin Y X, Xiao J P, Stone P R, Chamley L W
Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand; The Obstetrics and Gynaecology Hospital of Fudan University, China.
Wuxi Maternity and Children Health Hospital, Nanjing Medical University, China.
Placenta. 2015 Jun;36(6):661-6. doi: 10.1016/j.placenta.2015.03.009. Epub 2015 Apr 9.
Women with preeclampsia have elevated levels of inflammatory cytokines including IL-6. IL-6, which is known to activate endothelial cells and induce the production of necrotic trophoblastic debris from the placenta, may be important in the pathogenesis of preeclampsia. MgSO4 is a major therapy for the prevention of seizures in preeclampsia but it has been suggested to also have anti-inflammatory and vasodilatory properties.
22 pregnant women with preeclampsia and 68 normotensive controls were recruited and circulating IL-6 levels in these women were measured before MgSO4 and nifedipine treatment and after delivery. In addition, endothelial cells were treated with IL-6 or necrotic trophoblastic debris, generated from first trimester placental explants in the presence or absence of MgSO4in vitro, and cell-surface ICAM-1 was measured by ELISA. The levels of IL-6 in the culture medium were also measured. Furthermore nitric oxide synthetase activity in endothelial cells that had been treated with IL-6 was measured using l-NAME.
Circulating levels of IL-6 in preeclampsia were reduced significantly following administration of MgSO4. In vitro, MgSO4 reversed the activation of endothelial cells induced by IL-6 but not by necrotic trophoblastic debris. The effect of MgSO4 in reversing the IL-6 induced activation of endothelial cells was not dependent upon nitric oxide synthetase. Treating placental explants with MgSO4 prevented the production of necrotic trophoblastic debris induced by IL-6.
we demonstrated that IL-6 levels drop following treatment with MgSO4 and nifedipine in vivo, and have identified several mechanisms by which this positive effect on IL-6 may occur in vitro.
先兆子痫女性体内包括白细胞介素-6（IL-6）在内的炎性细胞因子水平升高。已知IL-6可激活内皮细胞并诱导胎盘产生坏死性滋养层碎片，其可能在先兆子痫的发病机制中起重要作用。硫酸镁（MgSO4）是预防先兆子痫惊厥的主要治疗方法，但也有人认为它还具有抗炎和血管舒张特性。
招募了22例先兆子痫孕妇和68例血压正常的对照者，在给予MgSO4和硝苯地平治疗前以及分娩后测量这些女性体内循环IL-6水平。此外，体外将内皮细胞用IL-6或坏死性滋养层碎片处理，坏死性滋养层碎片由孕早期胎盘外植体在有或无MgSO4的情况下产生，通过酶联免疫吸附测定法（ELISA）测量细胞表面细胞间黏附分子-1（ICAM-1）。还测量了培养基中IL-6的水平。此外，使用N-硝基-L-精氨酸甲酯（l-NAME）测量用IL-6处理过的内皮细胞中的一氧化氮合酶活性。
给予MgSO4后，先兆子痫患者体内循环IL-6水平显著降低。在体外，MgSO4可逆转IL-6诱导的内皮细胞活化，但不能逆转坏死性滋养层碎片诱导的内皮细胞活化。MgSO4逆转IL-6诱导的内皮细胞活化的作用不依赖于一氧化氮合酶。用MgSO4处理胎盘外植体可防止IL-6诱导产生坏死性滋养层碎片。
我们证明，体内给予MgSO4和硝苯地平治疗后IL-6水平下降，并确定了在体外可能发生这种对IL-6的积极作用的几种机制。
