Cornelius Denise C, Amaral Lorena M, Harmon Ashlyn, Wallace Kedra, Thomas Alexia J, Campbell Nathan, Scott Jeremy, Herse Florian, Haase Nadine, Moseley Janae, Wallukat Gerd, Dechend Ralf, LaMarca Babbette
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; and.
Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi; and.
Am J Physiol Regul Integr Comp Physiol. 2015 Oct 15;309(8):R884-91. doi: 10.1152/ajpregu.00154.2015. Epub 2015 Aug 19.
The reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits much of the pathology characterizing this disease, such as hypertension, inflammation, suppressed regulatory T cells (TRegs), reactive oxygen species (ROS), and autoantibodies to the ANG II type I receptor (AT1-AA) during pregnancy. The objective of this study was to determine whether supplementation of normal pregnant (NP) TRegs into RUPP rats would attenuate the pathophysiology associated with preeclampsia during pregnancy. CD4(+)/CD25(+) T cells were isolated from spleens of NP and RUPP rats, cultured, and injected into gestation day (GD) 12 normal pregnant rats that underwent the RUPP procedure on GD 14. On GD 1, mean arterial pressure (MAP) was recorded, and blood and tissues were collected for analysis. One-way ANOVA was used for statistical analysis. MAP increased from 99 ± 2 mmHg in NP (n = 12) to 127 ± 2 mmHg in RUPP (n = 21) but decreased to 118 ± 2 mmHg in RUPP+NP TRegs (n = 17). Circulating IL-6 and IL-10 were not significantly changed, while circulating TNF-α and IL-17 were significantly decreased after supplementation of TRegs. Placental and renal ROS were 339 ± 58.7 and 603 ± 88.1 RLU·min(-1)·mg(-1) in RUPP and significantly decreased to 178 ± 27.8 and 171 ± 55.6 RLU·min(-1)·mg(-1), respectively, in RUPP+NP TRegs; AT1-AA was 17.81 ± 1.1 beats per minute (bpm) in RUPP but was attenuated to 0.50 ± 0.3 bpm with NP TRegs. This study demonstrates that NP TRegs can significantly improve inflammatory mediators, such as IL-17, TNF-α, and AT1-AA, which have been shown to increase blood pressure during pregnancy.
子痫前期的降低子宫灌注压（RUPP）大鼠模型表现出该疾病的许多病理特征，如高血压、炎症、调节性T细胞（TRegs）受抑制、活性氧（ROS）以及孕期抗血管紧张素II 1型受体自身抗体（AT1-AA）。本研究的目的是确定将正常妊娠（NP）TRegs补充到RUPP大鼠中是否会减轻孕期与子痫前期相关的病理生理过程。从NP和RUPP大鼠的脾脏中分离出CD4(+)/CD25(+) T细胞，进行培养，然后注射到妊娠第12天且在第14天接受RUPP手术的正常妊娠大鼠体内。在妊娠第1天，记录平均动脉压（MAP），并采集血液和组织进行分析。采用单因素方差分析进行统计分析。MAP在NP组（n = 12）中从99 ± 2 mmHg升高至RUPP组（n = 21）中的127 ± 2 mmHg，但在RUPP + NP TRegs组（n = 17）中降至118 ± 2 mmHg。补充TRegs后，循环中的IL-6和IL-10无显著变化，而循环中的TNF-α和IL-17显著降低。RUPP组胎盘和肾脏的ROS分别为339 ± 58.7和603 ± 88.1 RLU·min(-1)·mg(-1)，在RUPP + NP TRegs组中显著降至178 ± 27.8和171 ± 55.6 RLU·min(-1)·mg(-1)；RUPP组中AT1-AA为17.81 ± 1.1次/分钟（bpm），而在NP TRegs组中减弱至0.50 ± 0.3 bpm。本研究表明，NP TRegs可显著改善炎症介质，如IL-17、TNF-α和AT1-AA，这些炎症介质已被证明会在孕期升高血压。
