Abstract：
Excessive activation of the mineralocorticoid receptor (MR) is implicated in cardiovascular and renal disease. Decreasing MR activation with MR antagonists (MRA) is effective to slow chronic kidney disease (CKD) progression and its cardiovascular comorbidities in animal models and patients. The present study evaluates the effects of the MR modulator balcinrenone and the MRA eplerenone on kidney damage in a metabolic CKD mouse model combining nephron reduction and a 60% high-fat diet. Balcinrenone and eplerenone prevented the progression of renal damages, extracellular matrix remodeling and inflammation to a similar extent. We identified a novel mechanism linking MR activation to the renal proteoglycan deposition and inflammation via the TLR4 pathway activation. Balcinrenone and eplerenone similarly blunted this pathway activation.
摘要：
盐皮质激素受体（MR）的过度激活与心血管和肾脏疾病有关。在动物模型和患者中，用MR拮抗剂（MRA）降低MR激活可有效减缓慢性肾脏疾病（CKD）的进展及其心血管合并症。本研究评估了结合肾单位减少和60％高脂饮食的代谢CKD小鼠模型中MR调节剂balcinenone和MRA依普利酮对肾脏损害的影响。Balcinrenone和eplerenone可预防肾脏损害的进展，细胞外基质重塑和炎症程度相似。我们确定了通过TLR4途径激活将MR激活与肾脏蛋白聚糖沉积和炎症联系起来的新机制。Balcinrenone和eplerenone同样减弱了该途径的激活。
