Faculty of Medicine, Universiti Teknologi MARA Sungai Buloh Campus, Selangor, Malaysia.
Faculty of Medicine, Universiti Teknologi MARA Sungai Buloh Campus, Selangor, Malaysia; I-PPerFORM, Universiti Teknologi MARA, Malaysia.
Reprod Biol. 2020 Jun;20(2):184-190. doi: 10.1016/j.repbio.2020.03.004. Epub 2020 Apr 3.
Levels of leptin and marinobufagenin (MBG), a cardiotonic steroid, are elevated in the serum of women with pre-eclampsia. Besides this, leptin administration to pregnant rats increases systolic blood pressure (SBP), urinary protein excretion and serum markers of endothelial activation. The link between leptin and MBG is unknown and it is also unclear if leptin-induced increases in blood pressure and proteinuria in the pregnant rat could be prevented by an MBG antagonist. To ascertain this link, this study investigated the effect of resibufogenin (RBG), a marinobufagenin antagonist, on leptin-induced increases in blood pressure and proteinuria during pregnancy in rats. Four groups of Sprague-Dawley rats, aged 12 weeks, were given either normal saline (CONTROL) or 120 μg/kg/day of leptin (LEP), or 120 μg/kg/day of leptin+30 μg/kg/day of resibufogenin (L + RBG) or 30 μg/kg/day of resibufogenin (RBG) from Day 1-20 of pregnancy. Systolic blood pressure and urinary protein excretion (UPE) were measured during the study period. Animals were euthanized on day 21 of pregnancy and vascular cell adhesion molecule 1, (VCAM-1), soluble intracellular cell adhesion molecule 1 (sICAM-1), E-selectin and endothelin-1 (ET-1) were estimated in the serum. SBP, UPE, VCAM-1, sICAM-1 and ET-1 were significantly higher only in the LEP group when compared with those in CONT and in L + RBG and RBG groups. The prevention by RBG of leptin-induced increases in SBP, proteinuria, and endothelial activation during pregnancy seem to suggest a potential role for MBG in leptin-induced adverse effects on blood pressure, urinary protein excretion and endothelial activity during pregnancy in the rat.
瘦素和海洋蟾蜍素（MBG）水平在先兆子痫妇女的血清中升高。此外，给怀孕大鼠施用瘦素会增加收缩压（SBP）、尿蛋白排泄和血清内皮激活标志物。瘦素与 MBG 之间的联系尚不清楚，也不清楚 MBG 拮抗剂是否可以预防怀孕大鼠中瘦素引起的血压升高和蛋白尿增加。为了确定这种联系，本研究调查了 resibufogenin（RBG），一种海洋蟾蜍素拮抗剂，对怀孕大鼠中瘦素诱导的血压和蛋白尿升高的影响。四组 12 周龄的 Sprague-Dawley 大鼠分别给予生理盐水（CONTROL）或 120 μg/kg/天的瘦素（LEP），或 120 μg/kg/天的瘦素+30 μg/kg/天的 resibufogenin（L + RBG）或 30 μg/kg/天的 resibufogenin（RBG）从怀孕第 1-20 天。在研究期间测量收缩压和尿蛋白排泄（UPE）。动物于怀孕第 21 天处死，测量血清中血管细胞粘附分子 1（VCAM-1）、可溶性细胞间粘附分子 1（sICAM-1）、E-选择素和内皮素-1（ET-1）。与 CONT 和 L + RBG 及 RBG 组相比，LEP 组的 SBP、UPE、VCAM-1、sICAM-1 和 ET-1 明显更高。RBG 对瘦素诱导的 SBP、蛋白尿和内皮激活增加的预防作用似乎表明 MBG 在瘦素诱导的血压升高、蛋白尿和怀孕大鼠内皮活性方面的潜在作用。
