关键词: 腹膜透析, 硫化氢, 腹膜纤维化, 腹膜间皮细胞转分化

Abstract:

Ｏｂｊｅｃｔｉｖｅ：To investigate the effect of exogenous hydrogen sulfide (H2S) on peritoneal morphological and functional damages in a rat model of peritoneal dialysis (PD).
Ｍｅｔｈｏｄｏｌｏｇｙ：A model of peritoneal fibrosis was established by intraperitoneally injecting 425%glucose peritoneal dialysis fluids (PDFs) and lipopolysaccharide (LPS) to SpragueDawley rats. And rats received daily intraperitoneal injections of NaHS (56 μg/kg), an H2S donor. After 28 days, peritoneal equilibration test (PET) was used to assess peritoneal function. Hematoxylin and eosin  and Massontrichrome staining were performed to observe pathological changes of parietal peritoneum. Immunohistochemical staining was used to detect αsmooth muscle actin (αSMA), type III collagen (ColⅢ) and transforming growth factorβ1 (TGFβ1). Synchronized confluent rat peritoneal mesothelial cells (PMCs) were incubated with 25%glucose PDFs with or without NaHS. The level of monocyte chemotactic protein1 (MCP1)、interleukin6 (IL6)、intercellular cell adhesion molecule1 (ICAM1)、αSMA、Ecadherin and TGFβ1 mRNA produced by PMCs were detected by RTPCR.
Ｒｅｓｕｌｔｓ： Compared with the control group, parietal peritoneum of the model rats under light microscopy exhibited thicker collagen accumulation, more neoangiogenesis and inflammatory cells infiltration (P<005). The expressions of ColⅢ, αSMA and TGFβ1 were significantly increased in the fibrotic peritoneum (P<005). Moreover, ultrafiltration volume (UV) of the PD model group was significantly decreased, while a higher peritoneal permeability reflected as a decrease of the D2/D0 glucose and an increase of the D2/P2 creatinine ratio (P<005). By contrast, administration of NaHS to the model rats, markedly decreased the inflammatory cells infiltration, neoangiogenesis and the biomarkers of fibrosis in the peritoneum (P<005), paralleled by reduced peritoneal permeability and increased ultrafiltration capacity (P<005). In cell culture experiments, exposure of rat PMCs to 25%glucose PDFs for 12 hours resulted in a significantly upregulated expression of MCP1, IL6, ICAM1 and TGFβ1 mRNA, which were attenuated by NaHS (P<001). Moreover, treatment with NaHS prevented 25%glucose PDFsinduced upregulated expression of αSMA and downgulated expression of Ecadherin in rat PMCs (P<001).
Ｃｏｎｃｌｕｓｉｏｎ：These findings suggest that, exogenous H2S is able to ameliorate peritoneal fibrosis and improve peritoneal transport function.

Key words: peritoneal dialysis, hydrogen sulfide, peritoneal fibrosis, epithelial-mesenchymal transition