Department of Nephrology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, China.
Deparment of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, China Shanghai, 200120, China.
BMC Nephrol. 2019 Nov 14;20(1):411. doi: 10.1186/s12882-019-1597-2.
Peritoneal fibrosis is the most common complication of peritoneal dialysis, but there is currently no effective treatment. We previously reported that suramin pretreatment prevents the development of peritoneal fibrosis in a rat model of peritoneal fibrosis induced by chlorhexidine gluconate (CG). Here, we further examined the effectiveness of delayed administration of suramin on peritoneal fibrosis and the mechanism (s) involved in this process.
In the rat model of peritoneal fibrosis induced by CG, suramin or saline was administered at day 21 and 28. All rats were then sacrificed to collect peritoneal tissues for Western blot analysis and histological staining at day 35.
Our results demonstrated that delayed administration of suramin starting at 21 days following CG injection can ameliorate peritoneal damage, with greater efficacy after two injections. Suramin also reduced the expression of α-smooth muscle actin, Collagen 1, and Fibronectin and suppressed phosphorylation of Smad-3, epidermal growth factor receptor (EGFR), signal transducers, activator of transcription 3 (STAT3) as well as extracellular signal-regulated kinases 1/2 (ERK 1/2) in the peritoneum injured with CG. Moreover, delayed administration of suramin inhibited overproduction of transforming growth factor-β1(TGF-β1) and expression of several pro-inflammatory cytokines, including monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-1, and interleukin-6.
Our results indicated that suramin can attenuate progression of peritoneal fibrosis by a mechanism involving inhibition of the TGF-β1/Smad3 and EGFR signaling pathways as well as suppression of multiple proinflammatory cytokines. Thus, suramin may have the potential to offer an effective treatment for peritoneal fibrosis.
腹膜纤维化是腹膜透析最常见的并发症，但目前尚无有效的治疗方法。我们之前报道过，苏拉明预处理可预防葡萄糖酸氯己定（CG）诱导的腹膜纤维化大鼠模型中腹膜纤维化的发展。在这里，我们进一步研究了苏拉明延迟给药对腹膜纤维化的有效性及其涉及的机制。
在 CG 诱导的腹膜纤维化大鼠模型中，在第 21 天和第 28 天给予苏拉明或生理盐水。所有大鼠在第 35 天处死，收集腹膜组织进行 Western blot 分析和组织学染色。
我们的结果表明，CG 注射后 21 天开始延迟给予苏拉明可以改善腹膜损伤，两次注射后效果更佳。苏拉明还降低了α-平滑肌肌动蛋白、胶原 1 和纤维连接蛋白的表达，并抑制了 CG 损伤腹膜中 Smad-3、表皮生长因子受体 (EGFR)、信号转导子和转录激活子 3 (STAT3)以及细胞外信号调节激酶 1/2 (ERK 1/2)的磷酸化。此外，延迟给予苏拉明抑制了转化生长因子-β1(TGF-β1)的过度产生和几种促炎细胞因子的表达，包括单核细胞趋化蛋白-1、肿瘤坏死因子-α、白细胞介素-1 和白细胞介素-6。
我们的结果表明，苏拉明通过抑制 TGF-β1/Smad3 和 EGFR 信号通路以及抑制多种促炎细胞因子，可减轻腹膜纤维化的进展。因此，苏拉明可能有潜力为腹膜纤维化提供有效的治疗。
