内源性调节性 T 细胞的增殖改善了与妊娠胎盘缺血相关的病理生理学。
Proliferation of endogenous regulatory T cells improve the pathophysiology associated with placental ischaemia of pregnancy.
机构信息
Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS, USA.
Experimental and Clinical Research Center, Berlin, Germany.
出版信息
Am J Reprod Immunol. 2017 Nov;78(5). doi: 10.1111/aji.12724. Epub 2017 Jul 6.
PROBLEM
Preeclampsia (PE) is associated with inflammation and decreased Treg cells and IL-10. The reduced uterine perfusion pressure (RUPP) rat model of PE exhibits these characteristics, and we hypothesized that induction of endogenous Tregs by a specific stimulus (CD28 superagonistic monoclonal antibody) would reduce inflammation, vasoactive factors, and hypertension in RUPP rats.
METHOD OF STUDY
RUPP was performed at gestation day (GD) 14; CD28 superagonist was administered intraperitoneally GD15; GD18 carotid catheters were inserted, and GD19 MAP and pup weight, blood, and tissues were collected.
RESULTS
MAP (mmHg) in NP rats was 99±5 and 122±2 in RUPPs and was 111±1 mmHg in RUPP+SA. Circulating Tregs were 6±2% in NP rats and 0.77±0.49% in RUPP rats but increased to 11± 3% in RUPP+SA rats. Circulating IL-6 and IL-2 were decreased while IL-10 and TGF-B were significantly increased in RUPP+SA compared to RUPP controls. Vasoactive pathways such as ET-1, AT1-AA, and ROS were all reduced in RUPP+SA compared to RUPP. Pup weight was 2.4±0.05 mg in NP and 1.94±0.062 mg in RUPP and increased to 2.1± 0.05 mg in RUPP+SA.
CONCLUSION
These data suggest that stimulating endogenous Tregs lower factors causing hypertension and can improve fetal weight in response to PE.
问题
子痫前期（PE）与炎症和调节性 T 细胞（Treg）和白细胞介素-10（IL-10）减少有关。PE 的 RUPP 大鼠模型表现出这些特征，我们假设通过特定刺激（CD28 超激动性单克隆抗体）诱导内源性 Treg 会减少 RUPP 大鼠的炎症、血管活性因子和高血压。
研究方法
在妊娠第 14 天（GD）进行 RUPP；在 GD15 时腹腔内给予 CD28 超激动剂；GD18 插入颈动脉导管，GD19 测量 MAP 和仔鼠体重、采集血液和组织。
结果
NP 大鼠的 MAP（mmHg）为 99±5 和 122±2，RUPP 大鼠为 111±1mmHg，RUPP+SA 大鼠为 111±1mmHg。循环 Treg 为 NP 大鼠的 6±2%和 RUPP 大鼠的 0.77±0.49%，但在 RUPP+SA 大鼠中增加到 11±3%。与 RUPP 对照组相比，RUPP+SA 大鼠的循环 IL-6 和 IL-2 降低，IL-10 和 TGF-B 显著增加。与 RUPP 相比，RUPP+SA 大鼠的血管活性途径如 ET-1、AT1-AA 和 ROS 均降低。NP 大鼠的仔鼠体重为 2.4±0.05mg，RUPP 大鼠为 1.94±0.062mg，RUPP+SA 大鼠增加到 2.1±0.05mg。
结论
这些数据表明，刺激内源性 Treg 可降低导致高血压的因素，并可改善 PE 胎儿的体重。
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