Peritoneal fibrosis (PF) is particularly common in individuals undergoing peritoneal dialysis (PD). Fibrosis of the parenchymal tissue typically progresses slowly. Therefore, preventing and reducing the advancement of fibrosis is crucial for effective patient treatment. Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF–PHI), primarily used to treat and improve renal anemia. Recent studies have found that HIF-1α possesses antioxidant activity and exerts a certain protective effect in ischemic heart disease and spinal cord injury, while it can also delay the progression of pulmonary and renal fibrosis. This study establishes the mice model through intraperitoneal injection of 4.25 % peritoneal dialysate fluid (PDF) and explores the therapeutic effects of Roxadustat by inducing TGF-β1-mediated endothelial-mesenchymal transition (EMT) in Met-5A cells. The aim is to investigate the protective role and mechanisms of Roxadustat against PD-related PF. We observed thicker peritoneal tissue and reduced permeability in animals with PD-related PF samples. This was accompanied by heightened inflammation, which Roxadustat alleviated by lowering the levels of inflammatory cytokines (IL-6, TNF-α). Furthermore, Roxadustat inhibited EMT in PF mice and TGF-β1-treated Met-5A cells, as evidenced by decreased expression of fibrotic markers, such as fibronectin, collagen I, and α-SMA, alongside an elevation in the expression of the epithelial marker, E-cadherin. Roxadustat also significantly decreased the expression of TGF-β1 and the phosphorylation of P-smad2 and P-smad3. In conclusion, Roxadustat ameliorates peritoneal fibrosis through the TGF-β/Smad pathway.

腹膜纤维化（PF）在接受腹膜透析（PD）的个体中尤其常见。实质组织的纤维化通常进展缓慢。因此，预防和减少纤维化的进展对于有效的患者治疗至关重要。 Roxadustat 是一种缺氧诱导因子脯氨酰羟化酶抑制剂 (HIF-PHI)，主要用于治疗和改善肾性贫血。近年来研究发现HIF-1α具有抗氧化活性，对缺血性心脏病和脊髓损伤具有一定的保护作用，同时还能延缓肺纤维化和肾纤维化的进展。本研究通过腹腔注射4.25%腹膜透析液（PDF）建立小鼠模型，并探讨Roxadustat通过诱导Met-5A细胞中TGF-β1介导的内皮间质转化（EMT）的治疗作用。目的是研究 Roxadustat 对 PD 相关 PF 的保护作用和机制。我们观察到，使用 PD 相关 PF 样本的动物腹膜组织变厚，渗透性降低。伴随着炎症加剧，Roxadustat 通过降低炎症细胞因子（IL-6、TNF-α）水平来缓解炎症。此外，Roxadustat 抑制 PF 小鼠和 TGF-β1 处理的 Met-5A 细胞中的 EMT，纤维化标记物（如纤连蛋白、胶原蛋白 I 和 α-SMA）表达减少，同时上皮标记物表达升高证明了这一点。 ， E-钙粘蛋白。 Roxadustat 还显着降低 TGF-β1 的表达以及 P-smad2 和 P-smad3 的磷酸化。总之，Roxadustat 通过 TGF-β/Smad 途径改善腹膜纤维化。