Tanshinone IIA attenuates peritoneal fibrosis through inhibition of fibrogenic growth factors expression in peritoneum in a peritoneal dialysis rat model

摘要

Background: Peritoneal fibrosis is a common complication of long-term peritoneal dialysis (PD) and is the main cause of dialysis inadequacy and PD withdrawal. It has been reported that Tanshinone IIA can ameliorate fibrosis in various tissues. In this report, we investigate the effects of Tanshinone IIA on peritoneal fibrosis in an animal model. Methods: Forty rats were randomly divided into four groups (n10 per group) that received daily intraperitoneal injection of saline, 4.25% glucose-based peritoneal dialysis fluid (PDF), or PDF along with 50 or 100 mg/L Tanshinone IIA. Eight weeks later, the rats were sacrificed and peritoneal tissue samples were collected for analysis. The expression of transforming growth factor-β=1 (TGF-β=1) and connective tissue growth factor (CTGF) in parietal peritoneum was examined by immunohistochemistry. The mRNA and protein expression of TGF-β=1 and CTGF in omentum was examined by reverse transcription polymerase chain reaction or Western blot. Results: Tanshinone IIA significantly suppressed submesothelial compact zone thickening and matrix accumulation induced by 4.25% glucose-based PDF. Tanshinone IIA also reduced TGF-β=1 and CTGF expression in parietal peritoneum as well as in omentum in a dose-dependent manner. Conclusion: Tanshinone IIA prevented the progression of peritoneal fibrosis in this rat model. Tanshinone IIA may be a novel therapy for peritoneal fibrosis in patients undergoing long-term PD.