Morgaan Hagar A, Sallam Marwa Y, El-Deeb Nevine M, El-Gowelli Hanan M, El-Gowilly Sahar M, El-Mas Mahmoud M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alazarita 21521, Alexandria, Egypt.
Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Sci Rep. 2025 Mar 8;15(1):8137. doi: 10.1038/s41598-025-87586-4.
Preeclampsia (PE) and peripartum sepsis are two complications of pregnancy and are often associated with disturbed renal function due possibly to dysregulated renin angiotensin system. Here we evaluated hemodynamic and renal consequences of separate and combined PE and sepsis insults in weaning mothers and tested whether this interaction is influenced by prenatally-administered losartan (AT1-receptor blocker) or pioglitazone (PPARγ agonist). The PE-rises in blood pressure and proteinuria induced by gestational nitric oxide synthase inhibition (L-NAME, 50 mg/kg/day for 7 days) were attenuated after simultaneous treatment with losartan or pioglitazone. These drugs further improved glomerular and tubular structural defects and impaired vasodilatory responses evoked by adenosinergic (N-ethylcarboxamidoadenosine) or cholinergic (acetylcholine) receptor activation in perfused kidneys of weaning dams. Likewise, treatment of weaning PE dams with a single 4-h dosing of lipopolysaccharides (LPS, 5 mg/kg) weakened renal structural damage, enhanced renal vasodilations and accentuated the upregulated vasodilatory response set off by losartan or pioglitazone. Molecularly, the favorable effect of pharmacologic or endotoxic intervention was coupled with dampened tubular and glomerular expressions of inflammatory (toll-like receptor 4) and apoptotic signals (caspase-3). Our data unveil beneficial and possibly intensified conditioning effect for endotoxemia when combined with losartan or pioglitazone against preeclamptic renovascular dysfunction and inflammation.
子痫前期（PE）和围产期败血症是妊娠的两种并发症，可能由于肾素血管紧张素系统失调而常伴有肾功能紊乱。在此，我们评估了断奶母鼠单独及联合发生PE和败血症损伤时的血流动力学和肾脏后果，并测试了这种相互作用是否受产前给予的氯沙坦（AT1受体阻滞剂）或吡格列酮（PPARγ激动剂）影响。妊娠期间一氧化氮合酶抑制（L-NAME，50mg/kg/天，持续7天）诱导的PE血压升高和蛋白尿，在同时使用氯沙坦或吡格列酮治疗后减弱。这些药物进一步改善了断奶母鼠灌注肾脏中由腺苷能（N-乙基羧酰胺腺苷）或胆碱能（乙酰胆碱）受体激活引起的肾小球和肾小管结构缺陷及受损的血管舒张反应。同样，用单剂量脂多糖（LPS，5mg/kg）对断奶PE母鼠进行4小时给药治疗，减弱了肾脏结构损伤，增强了肾血管舒张，并增强了氯沙坦或吡格列酮引发的上调血管舒张反应。在分子水平上，药理或内毒素干预的有益作用与炎症（Toll样受体4）和凋亡信号（半胱天冬酶-3）在肾小管和肾小球的表达减弱相关。我们的数据揭示了与氯沙坦或吡格列酮联合使用时，对内毒素血症针对子痫前期肾血管功能障碍和炎症具有有益且可能增强的调节作用。
