Cardiovascular and renal inflammation induced by Aldosterone (Aldo) plays a pivotal role in the pathogenesis of hypertension and renal fibrosis. GSK-3β contributes to inflammatory cardiovascular and renal diseases, but its role in Aldo-induced hypertension, and renal damage is not clear. In the present study, rats were treated with Aldo combined with SB-216763 (a GSK-3β inhibitor) for 4 weeks. Hemodynamic, cardiac, and renal parameters were assayed at the indicated time. Here we found that rats treated with Aldo presented cardiac and renal hypertrophy and dysfunction. Cardiac and renal expression levels of molecular markers attesting inflammation and fibrosis were increased by Aldo infusion, whereas the treatment of SB-216763 reversed these alterations. SB-216763 suppressed cardiac and renal inflammatory cytokines levels (TNF-a, IL-1β, and MCP-1). Meanwhile, SB-216763 increased the protein levels of LC3-II in the cardiorenal tissues as well as p62 degradation, indicating that SB-216763 induced autophagy activation in cardiac, and renal tissues. Importantly, inhibition of autophagy by 3-MA attenuated the role of SB-216763 in inhibiting perivascular fibrosis, and tubulointerstitial injury. These data suggest that SB-216763 protected against Aldo-induced cardiac and renal injury by activating autophagy, and might be a therapeutic option for salt-sensitive hypertension and renal fibrosis.

中文翻译：

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SB-216763是GSK-3β抑制剂，可通过激活自噬保护醛固酮诱导的心脏和肾脏损伤。

醛固酮（Aldo）诱发的心血管和肾脏炎症在高血压和肾纤维化的发病机理中起着关键作用。GSK-3β有助于炎症性心血管疾病和肾脏疾病，但其在Aldo诱发的高血压中的作用以及肾损害尚不清楚。在本研究中，大鼠接受Aldo联合SB-216763（一种GSK-3β抑制剂）治疗4周。在指定的时间测定血流动力学，心脏和肾脏参数。在这里，我们发现用Aldo治疗的大鼠表现出心脏和肾脏肥大和功能障碍。通过Aldo输注，证明炎症和纤维化的分子标志物的心脏和肾脏表达水平增加，而SB-216763的治疗逆转了这些改变。SB-216763抑制了心脏和肾脏炎性细胞因子的水平（TNF-α，IL-1β和MCP-1）。同时，SB-216763增加了心肾组织中LC3-II的蛋白水平以及p62降解，表明SB-216763诱导了心脏和肾脏组织中的自噬激活。重要的是，3-MA对自噬的抑制作用减弱了SB-216763在抑制血管周围纤维化和肾小管间质损伤中的作用。这些数据表明，SB-216763可通过激活自噬来防止Aldo引起的心脏和肾脏损伤，并且可能是盐敏感性高血压和肾纤维化的治疗选择。3-MA对自噬的抑制减弱了SB-216763在抑制血管周围纤维化和肾小管间质损伤中的作用。这些数据表明，SB-216763可通过激活自噬来防止Aldo引起的心脏和肾脏损伤，并且可能是盐敏感性高血压和肾纤维化的治疗选择。3-MA对自噬的抑制减弱了SB-216763在抑制血管周围纤维化和肾小管间质损伤中的作用。这些数据表明，SB-216763可通过激活自噬来防止Aldo引起的心脏和肾脏损伤，并且可能是盐敏感性高血压和肾纤维化的治疗选择。