This study investigated the effect of apela on renal function and anti-inflammatory effect on whole body and kidney tissue in mice with type I cardiorenal syndrome (CRS). The murine type I CRS model was established and apela was subcutaneously infused for two weeks. Cardiac and renal functions were evaluated by echocardiography and blood biochemistry, respectively. The systemic and renal inflammatory responses were examined with molecular biological and histological methods. Human renal glomerular endothelial cells (RGECs) were used to evaluate the adhesion effect of monocytes in vitro. Compared to mice from the control group (CRS + vehicle), the plasma levels of N-terminal pro-brain natriuretic peptide, blood urea nitrogen and creatinine were significantly decreased, while the mean left ventricular ejection fraction was increased in apela-treated CRS mice at the 4th week. The expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in the circulation and kidney was decreased in apela-treated mice compared with control mice, and apela improved cardio-renal pathology in mice with type I CRS. Additionally, Apela significantly suppressed the expression of MCP-1, TNF-α, intercellular adhesion molecule-1 and vascular intercellular adhesion molecule-1 in RGECs induced by angiotensin II (Ang II), and inhibited the promoting effect of Ang II on the adhesion of THP-1 cells to RGECs. Western blot results showed that the expression of phosphorylated nuclear factor kappa B (phospho-NFκB) in CRS mice was increased, but the expression of phospho-NFκB was down-regulated after apela treatment. Furthermore, apela significantly inhibited the Ang II-mediated increase in phospho-NFκB expression in RGECs in vitro, but the administration of an apelin peptide jejunum receptor (APJ) inhibitor blocked the inhibitory effect of apela. This study revealed that apela improves cardiorenal function and reduces systemic and renal inflammatory response in type I CRS mice and the apela/APJ system may alleviate renal inflammatory responses by inhibiting the NFκB signalling pathway.

中文翻译：

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Apela 抑制 I 型心肾综合征小鼠的全身和肾脏炎症反应

本研究探讨apela对I型心肾综合征（CRS）小鼠肾功能的影响以及对全身和肾组织的抗炎作用。建立小鼠I型CRS模型，皮下注射apela两周。分别通过超声心动图和血液生化评估心脏和肾脏功能。用分子生物学和组织学方法检查全身和肾脏炎症反应。人肾小球内皮细胞 (RGEC) 用于评估体外单核细胞的粘附作用。与对照组（CRS+载体）小鼠相比，血浆N端脑钠肽前体、血尿素氮和肌酐水平显着降低，而在第 4 周，apela 治疗的 CRS 小鼠的平均左心室射血分数增加。与对照小鼠相比，apela 治疗小鼠循环和肾脏中单核细胞趋化蛋白-1 (MCP-1) 和肿瘤坏死因子-α (TNF-α) 的表达降低，apela 改善了小鼠的心肾病理与 I 型 CRS。此外，Apela显着抑制血管紧张素II（Ang II）诱导的RGECs中MCP-1、TNF-α、细胞间粘附分子-1和血管细胞间粘附分子-1的表达，并抑制Ang II对粘附的促进作用。 THP-1 细胞转化为 RGEC。Western blot结果显示，CRS小鼠磷酸化核因子κB（phospho-NFκB）的表达增加，但apela处理后磷酸化NFκB的表达下调。此外，apela 显着抑制了体外 RGEC 中 Ang II 介导的磷酸化 NFκB 表达的增加，但 apelin 肽空肠受体 (APJ) 抑制剂的给药阻断了 apela 的抑制作用。本研究表明，apela 可改善 I 型 CRS 小鼠的心肾功能并减少全身和肾脏炎症反应，apela/APJ 系统可能通过抑制 NFκB 信号通路减轻肾脏炎症反应。