Wang Yong, Wang Hao, Lu Huiqing, Ma Ji, Wu Wei, Wang Yinan, Ma Bo, Zhu Hao, Hu Rong
The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Sci Rep. 2025 Jan 6;15(1):915. doi: 10.1038/s41598-025-85258-x.
Preeclampsia (PE) is a prevalent and severe pregnancy complication that significantly impacts maternal and perinatal health. Epidemiological studies and animal experiments have demonstrated that PE adversely affects the cardiovascular and nervous systems of offspring, increasing their risk of hypertension and renal pathology. However, the mechanisms underlying this increased risk remain unclear. This study utilized an L-NAME-induced preeclampsia mouse model (PELS model) to investigate the effects of PE on offspring blood pressure and renal pathology, focusing on the expression of Angiotensin II Type 1 Receptors (AT1R) and related molecules in renal tissues. Our findings show that L-NAME-induced pre-eclampsia led to reduced birth weights and significantly elevated systolic blood pressure in 6-week-old offspring. Histopathological analysis revealed pronounced glomerular and tubular damage in the kidneys of both 1-week and 6-week-old offspring from the pre-eclampsia group. At 1 week of age, the pre-eclampsia group exhibited elevated mRNA and protein expression levels of AT1R, GRK4, AQP2, ENaC, and NCC in renal tissues compared to controls. However, these differences were no longer significant at 6 weeks of age. No significant gender differences were observed in either blood pressure or renal pathological changes. Preeclampsia induced by L-NAME results in increased blood pressure and renal damage in offspring, potentially mediated by early alterations in the renal RAS system. The observed changes in AT1R and related molecules appear to be transient, suggesting that the early impact of pre-eclampsia on renal structure may trigger, but not sustain, hypertension in offspring. Further studies are needed to elucidate the long-term mechanisms driving hypertension in this population.
子痫前期（PE）是一种常见且严重的妊娠并发症，对孕产妇和围产期健康有重大影响。流行病学研究和动物实验表明，PE会对后代的心血管和神经系统产生不利影响，增加其患高血压和肾脏病变的风险。然而，这种风险增加的潜在机制仍不清楚。本研究利用L-NAME诱导的子痫前期小鼠模型（PELS模型），研究PE对后代血压和肾脏病变的影响，重点关注肾组织中血管紧张素II 1型受体（AT1R）及相关分子的表达。我们的研究结果表明，L-NAME诱导的子痫前期导致出生体重降低，且6周龄后代的收缩压显著升高。组织病理学分析显示，子痫前期组1周龄和6周龄后代的肾脏均有明显的肾小球和肾小管损伤。在1周龄时，子痫前期组肾组织中AT1R、GRK4、AQP2、ENaC和NCC的mRNA和蛋白表达水平高于对照组。然而，这些差异在6周龄时不再显著。在血压或肾脏病理变化方面未观察到明显的性别差异。L-NAME诱导的子痫前期会导致后代血压升高和肾脏损伤，可能由肾脏肾素-血管紧张素系统（RAS）的早期改变介导。观察到的AT1R及相关分子的变化似乎是短暂的，这表明子痫前期对肾脏结构的早期影响可能引发但不能维持后代的高血压。需要进一步研究来阐明该人群高血压的长期发病机制。
