Impact of Rapamycin on Peritoneal Fibrosis and Transport Function

Abstract

Objectives: To observe the impact of rapamycin on peritoneal fibrosis and peritoneal transport function in a rat model of peritoneal fibrosis. Methods: A total of 40 male SD rats were randomly divided into five groups, with 8 rats in each group. Group N was the normal control. In group NS, the rats were injected daily with 20 ml of saline intraperitoneally. In groups GLU, L-RAPA and H-RAPA, rats were injected daily with 20 ml of 4.25% peritoneal dialysis solution intraperitoneally, together with 150 µg of lipopolysaccharide on days 1, 3, 5 and 7. Rapamycin was administered to groups L-RAPA (250 µg/day) and H-RAPA (500 µg/day) intragastrically. On days 21 and 35, 4 rats from each group were selected to evaluate their peritoneal transport function (ultrafiltration volume, D₂/D₀ ratio). The parietal peritoneal membrane from the rats was used for pathological study. Light microscopy (HE staining and VG staining) was used to assess the morphological changes. The expression levels of Col I, α-SMA, TGF-β₁, Reca and Ki67 in the parietal peritoneal membrane were observed by immunohistochemistry. Results: The ultrafiltration volume and D₂/D₀ ratio decreased in group GLU compared with group N on day 21 (p < 0.05) and further decreased on day 35 (p < 0.01), whereas such a significant change was not observed in group L-RAPA or H-RAPA. Furthermore, severe loss of the peritoneal mesothelial cells, exposure of the collagen matrix under the mesothelial cells, and infiltration of fibroblasts and various inflammatory cells were detected in group GLU on days 21 and 35. The thickness of the submesothelial compact zone significantly increased in group GLU compared with group N (p < 0.01). However, in groups L-RAPA and H-RAPA, the morphological changes were clearly alleviated, and the submesothelial compact zone was thinner than in group GLU (p < 0.01). The expression levels of Col I, α-SMA, TGF-β₁, Ki67 and Reca in the peritoneal membrane were significantly increased in group GLU compared with group N on days 21 and 35 (p < 0.01), whereas these changes were significantly attenuated in groups L-RAPA and H-RAPA compared with group GLU (p < 0.01). Conclusions: Rapamycin had an obvious effect in inhibiting peritoneal fibrosis and improving peritoneal membrane transport function.