高盐饮食通过激活盐皮质受体引发Dahl SS大鼠肾损伤和高血压的新机制  

A Novel Mechanism of High-Salt Diet Trigger Renal Injury and Hypertension in Dahl SS Rats by Activating Mineralocorticoid Receptor

作　　者：李曦 王蕊 李洪林 LI Xi;WANG Rui;LI Honglin(Shanghai Key Laboratory of New Drug Design,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学药学院,上海市新药设计重点实验室,上海200237

出　　处：《华东理工大学学报（自然科学版）》2024年第3期391-399,共9页Journal of East China University of Science and Technology

摘　　要：盐敏感高血压作为一种顽固性高血压,其发病机制十分复杂。虽然盐皮质激素受体激活和肾损伤在盐敏感高血压的发展中起关键作用,但具体的病理机制目前并不明确。通过高盐饮食诱导建立达尔盐敏感(Dahl SS)大鼠高血压模型,探究盐敏感高血压及肾损伤产生的病理机制。与盐不敏感的SS-13BN大鼠相比,长期高盐饮食会造成Dahl SS大鼠肾脏中交感神经和肾素-血管紧张素-醛固酮系统(RAAS)的局部激活,最终激活盐皮质激素受体(MR),导致上皮钠通道(ENaC)表达增加、氧化应激与炎症反应增强,从而发生肾纤维化病变,并引发肾脏中磷酸化肌动蛋白(P-Cofilin)与足蛋白(Podocin)表达增加,造成足细胞损伤,最终引发肾损伤与高血压症状。As a resistant hypertension,the pathogenesis of salt-sensitive hypertension is complex.Although mineralocorticoid receptor activation and renal injury play a key role in the development of salt-sensitive hypertension,the specific pathological mechanism is currently unclear.A model of Dahl SS hypertension was established by high-salt diet induction to explore the pathological mechanism of salt-sensitive hypertension and kidney injury.Compared with salt-insensitive SS-13BN rats,long-term high-salt diet caused local activation of sympathetic nerves and reninangiotensin-aldosterone system(RAAS)in the kidney of Dahl SS rats,which eventually activated mineralocorticoid receptors(MR),resulting in the increased expression of epithelial sodium channels(ENaC),enhanced inflammatory response and oxidative stress,renal fibrosis,and triggered the increased expression of phosphorylated actin(P-Cofilin)and podocin in the kidney,resulting in podocyte damage and ultimately renal injury and hypertension.

关 键 词：高盐饮食 Dahl SS大鼠 盐敏感高血压 肾损伤 盐皮质激素受体 

分 类 号：R965[医药卫生—药理学]