Introduction Cardiovascular disease constitutes the leading cause of mortality in patients with chronic kidney disease (CKD), which is termed cardiorenal syndrome type 4 (CRS-4). Here, we report the development of pathological cardiac remodeling and fibrosis in unilateral urinary obstruction (UUO) rats. Methods Hematoxylin and eosin (H&E) staining was performed to observe the pathology of myocardial tissue. The degree of myocardial tissue fibrosis was observed by Masson and Sirius red staining. Immunohistochemical staining was applied to detect the expression of CD34 and CD105 in myocardial tissue, and immunofluorescent staining was performed to examine the expression of CD34, collagen I/collagen III, and alpha smooth muscle actin (α-SMA). The expression of the signal pathway-related proteins vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), nuclear factor κB (NF-κB), and interleukin (IL)-1β was tested by western blotting. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of serum and glucocorticoid-inducible kinase (SGK)-1, NF-κB, and interleukin-1β (IL-1β). Results The results showed the development of pathological cardiac remodeling and cardiac dysfunction in UUO rats. Moreover, there was more angiogenesis and endothelial-mesenchymal transition (End-MT) in the UUO group, and these effects were inhibited by eplerenone. Conclusions The results indicated that this cardiac fibrosis was associated with angiogenesis and that End-MT was related to aldosterone and mineralocorticoid receptor (MR) activation. Moreover, in association with the MR/IL-1β/VEGFA signaling pathway, early treatment with the MR antagonist eplerenone in rats with UUO-induced CKD may significantly attenuate MR activation and cardiac fibrosis.

中文翻译：

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依普利酮通过抑制单侧尿路梗阻大鼠的血管生成来预防心脏纤维化。

引言 心血管疾病是慢性肾脏病 (CKD) 患者死亡的主要原因，称为 4 型心肾综合征 (CRS-4)。在这里，我们报告了单侧尿路梗阻 (UUO) 大鼠病理性心脏重塑和纤维化的发展。方法采用苏木精伊红(H&E)染色观察心肌组织病理学。Masson和Sirius红染色观察心肌组织纤维化程度。免疫组化染色检测心肌组织中CD34和CD105的表达，免疫荧光染色检测CD34、胶原I/胶原III和α-平滑肌肌动蛋白（α-SMA）的表达。信号通路相关蛋白血管内皮生长因子A（VEGFA）的表达，通过蛋白质印迹检测血管内皮生长因子受体 2 (VEGFR2)、核因子 κB (NF-κB) 和白细胞介素 (IL)-1β。逆转录聚合酶链反应 (RT-PCR) 用于检测血清和糖皮质激素诱导激酶 (SGK)-1、NF-κB 和白细胞介素-1β (IL-1β) 的 mRNA 水平。结果结果显示UUO大鼠发生病理性心脏重构和心功能不全。此外，UUO 组有更多的血管生成和内皮间质转化（End-MT），这些作用被依普利酮抑制。结论 结果表明，这种心脏纤维化与血管生成有关，而 End-MT 与醛固酮和盐皮质激素受体 (MR) 的激活有关。此外，与 MR/IL-1β/VEGFA 信号通路相关，