17-Hydroxyprogesterone caproate improves T cells and NK cells in response to placental ischemia; new mechanisms of action for an old drug
17-Hydroxyprogesterone caproate improves T cells and NK cells in response to placental ischemia; new mechanisms of action for an old drug
复制标题
DOI：
10.1016/j.preghy.2019.11.005
复制
发表时间：
2020-01-01
影响因子：
2.2
通讯作者：
Amaral, Lorena M.
中科院分区：
文献类型：
--
作者：
Elfarra, Jamil T.;Cottrell, Jesse N.;Amaral, Lorena M.
先兆子痫 (PE) 是妊娠期间新发的高血压，与子宫动脉阻力 (UARI) 增加以及 CD4 + T 淋巴细胞和自然杀伤 (NK) 细胞之间的不平衡有关。我们在 RUPP 大鼠 PE 模型中证明了 17-羟基孕酮己酸酯 (17-OHPC) 在改善高血压和胎儿死亡方面的重要作用。然而，我们尚未研究 17-OHPC 改善 NK 细胞和 CD4(+)TH2 细胞的作用，作为改善胎儿体重和高血压的可能机制。因此，我们假设 17-OHPC 会降低 NK 细胞，同时提高 RUPP 大鼠中的 T 细胞比例。在妊娠第 14 天对怀孕大鼠进行手术诱导 RUPP。第 15 天腹膜内给予 17-OHPC (3.32 mg/kg)，第 18 天测量 UARI。在 GD 19 收集血压 (MAP)、血液和组织。NP 大鼠 (n = 9) 中的 MAP 为 100 +/- 2，Sham 大鼠 (n = 8) 中为 104 +/- 6，RUPP (n = 11) 中为 128 +/- 2 RUPP + 17-OHPC 中为 115 +/- 3 mmHg (n = 10)，p < 0.05。 17-OHPC 后幼仔体重和 UARI 均得到改善。 RUPP 大鼠中胎盘 NK 细胞总数和溶细胞性胎盘 NK 细胞分别为 38 +/- 5 和 12 +/- 2% 门，而 RUPP + 17OHPC 大鼠中则降至 1.6 +/- 0.5 和 0.4 +/- 0.2% 门。 RUPP大鼠中CD4(+) T细胞为40+/-3，RUPP+17-OHPC大鼠显着下降至7+/-1。 RUPP 大鼠中循环和胎盘 TH2 细胞为 6.0 +/- 1、0.3 +/- 0.1% 门控，RUPP + 17-OHPC 大鼠中为 12 +/- 1%、2 +/- 0.5% 门控，p < 0.05 这项研究确定了 17-OHPC 改善胎盘缺血结局的新机制。
Preeclampsia (PE) is new onset hypertension during pregnancy associated with increased uterine artery resistance (UARI) and an imbalance among CD4 + T lymphocytes and natural killer (NK) cells. We have shown an important role for 17-hydroxyprogesterone caproate (17-OHPC) to improve hypertension and fetal demise in the RUPP rat model of PE. However we have not examined a role for 17-OHPC to improve NK cells and CD4(+)TH2 cells as possible mechanisms for improved fetal weight and hypertension. Therefore, we hypothesized that 17-OHPC lowers NK cells while improving the T cell ratio in the RUPP rat. RUPP was surgically induced on gestational day 14 in pregnant rats. 17-OHPC (3.32 mg/kg) was administered intraperitoneal on day 15, UARI was measured on day 18. Blood pressure (MAP), blood and tissues were collected on GD 19. MAP in NP rats (n = 9) was 100 +/- 2, 104 +/- 6 in Sham rats (n = 8), 128 +/- 2 in RUPP (n = 11) and 115 +/- 3 mmHg in RUPP + 17-OHPC (n = 10), p < 0.05. Pup weight and UARI were improved after 17-OHPC. Total and cytolytic placental NK cells were 38 +/- 5, and 12 +/- 2% gate in RUPP rats which decreased to 1.6 +/- 0.5 and 0.4 +/- 0.2% gate in RUPP + 17OHPC rats. CD4(+) T cells were 40 +/- 3 in RUPP rats, which significantly decreased to 7 +/- 1 RUPP + 17-OHPC rats. Circulating and placental TH2 cells were 6.0 +/- 1, 0.3 +/- 0.1% gate in RUPP rats and 12 +/- 1%, 2 +/- 0.5% gate in RUPP + 17-OHPC rats, p < 0.05 This study identifies new mechanisms whereby 17-OHPC improves outcomes in response to placental ischemia.