Background: Sairei-to is a herbal prescription originating from traditional Chinese medicine. We conducted an experimental study on rat peritoneal fibrosis to clarify the suppressive mechanisms of sairei-to. Methods: Wistar rats were intraperitoneally injected with chlorhexidine gluconate (CG) every day. Peritoneal specimens were collected after 28 days of CG injection and oral administration of sairei-to. Macrophage infiltration, extracellular matrix accumulation, and angiogenesis were evaluated by immunostaining for ED-1, fibronectin, and CD-31, respectively. To observe oxidative stress in the tissue, 4-hydroxy-2-noneal (HNE) accumulation and plasma levels of superoxide dismutase (SOD) activity were detected. As a candidate of antioxidative components in sairei-to, plasma levels of baicalin were determined by high-performance liquid chromatography. Results: Compared with the disease control group, serum total protein levels were significantly recovered in the sairei-to treatment group. Thickness of the submesothelial compact zone, trichrome-stained area, ED-1-positive cells, fibronectin-staining area, and HNE accumulation were suppressed in the treatment group. Concurrently, decreased plasma levels of SOD activity were recovered by sairei-to treatment. Increased CD-31-positive vessel number and area were also suppressed in the sairei-to group. Baicalin was detected in the plasma samples of the sairei-to group at 0.29 ± 0.11 µg/ml (mean±SEM). Conclusion: These results suggest that sairei-to ameliorates peritoneal fibrosis, partly through suppressing oxidative stress and macrophage infiltration.

Objective Fibrin deposition on the peritoneum has been frequently observed in peritoneal fibrosis induced by long-term peritoneal dialysis. The present study was conducted to clarify the contribution of factor Xa through tissue factor and factor V expression in peritoneal fibrosis. Methods Wistar rats were intraperitoneally injected with chlorhexidine gluconate (CG) every day. For the interventional study, the factor Xa inhibitor fondaparinux was subcutaneously administered. After 28 days of CG injection, peritoneal specimens were examined by immunohistochemical analyses and in situ hybridization. Results The peritoneal submesothelial compact zone was observed to be markedly thicker in the CG-injected groups than in the normal group, and that thickness was dose dependent. Immunohistochemical study revealed massive fibrin, fibronectin, and type IV collagen depositions in the CG-injected groups, which was markedly higher than that in the normal group. Macrophage infiltration and staining for tissue factor, factor V, factor X, and protease-activated receptor-2 were intense in the CG-injected groups and negative/trace in the normal group. Tissue factor and factor V mRNAs were abundant in cells in the thickened peritoneum. A double-labeling experiment revealed that tissue factor was observed mainly in macrophages, and factor V was abundantly distributed in the fibrotic tissue together with macrophages. Fondaparinux treatment decreased the thickness of submesothelial fibrotic tissue, and size and number of CD31-positive vessels. Conclusion These results suggest that expression of tissue factor and factor V in infiltrated macrophages, together with factor X deposition, may progress angiogenesis and accumulation of extracellular matrix components, partly via profibrotic and procoagulant mechanisms in the peritoneum after inflammatory stimulation.