Eplerenone ameliorates lung fibrosis in unilateral ureteral obstruction rats by inhibiting lymphangiogenesis

作者：Ziqian Liu, Cuijuan Zhang, Juan Hao, Gege Chen, Lingjin Liu, Yunzhao Xiong, Yi Yao Chang, Hui Li, Tatsuo Shimosawa, Fan Yang, Qingyou Xu · 发表于：Experimental and Therapeutic Medicine · 年份：2022 · DOI：10.3892/etm.2022.11560 · 被引用次数：7 · 研究领域：Lymphatic System and Diseases、Lymphatic Disorders and Treatments、Neonatal Respiratory Health Research

Chronic kidney disease (CKD) involves progressive and irreversible loss of renal function, often causing complications and comorbidities and impairing the function of various organs. In particular, lung injury is observed not only in advanced CKD but also in early-stage CKD. The present study investigated the potential involvement of mineralocorticoid receptors (MRs) and lymphatic vessels in lung injury using a 180-day unilateral ureteral obstruction (UUO) model for CKD. Changes in lung associated with lymphangiogenesis and inflammatory were analyzed in UUO rats. The pathology of the lung tissue was observed by hematoxylin and eosin and Masson's staining. Detection of the expression of lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1), Podoplanin, vascular endothelial growth factor receptor-3 (VEGFR-3) and VEGF C to investigate lymphangiogenesis. The mRNA and protein expression levels of IL-1β, monocyte chemotactic protein 1, tumor necrosis factor-α, nuclear factor κB, phosphorylated serum and glucocorticoid-induced protein kinase-1 and MR were evaluated using western blot, reverse transcription-quantitative PCR, immunohistochemical staining and immunofluorescence staining. In the present study, long-term UUO caused kidney damage, which also led to lung inflammation, accompanied by lymphangiogenesis. However, treatment with eplerenone, an MR blocker, significantly reduced the severity of lung injury and lymphangiogenesis. Therefore, lymphangiogenesis contribute...