Inhibitory effect of melatonin on peritoneal fibrosis in rats and its mechanism

Objective To investigate the inhibitory effect and the mechanism of melatonin on peritoneal fibrosis in rats.Methods Forty-five male SD rats were randomly divided into 3 groups (n=15 each). The control group was intraperitoneally injected with normal saline (1.0 ml·100 g^-1·day^-1). Model group was intraperitoneally injected with 0.1% chlorhexidine gluconate (1.0 ml·100 g^-1·day^-1). Model and melatonin group was intraperitoneally injected with 0.1% glucose (1.0 ml·100 g^-1·day^-1) and melatonin (5.0 mg·kg^-1·day^-1) dissolved in 0.5 ml 0.9% normal saline simultaneously. The ultrafiltration volume was measured after 14 days. The rats were then sacrificed and the peritoneal tissue was obtained. HE staining was used to observe the morphological changes of peritoneal tissue. The expression of TGF-β1 in parietal peritoneum was detected by immunohistochemistry. Western blotting was applied to detect the expression of p-Smad2/3 and Smad7 proteins in visceral peritoneum.Results As compared with the control group, the peritoneal ultrafiltration volume in the model group was decreased, and the peritoneal thickness was significantly increased. In the model group, peritoneal fibrosis presented as mesothelial cell disorder, subcutaneous collagen fiber deposition, inflammatory cell infiltration, etc. What's more, the expression of TGF-β1, p-Smad2, Smad7 protein was significantly increased. As compared with the model group, the peritoneal ultrafiltration volume in the model+melatonin group was improved, the peritoneal fibrosis was alleviated, the peritoneal tissue was thinned, and the expression of TGF-β1, p-Smad2/3 and Smad7 protein was significantly decreased.Conclusions Melatonin can inhibit the progress of peritoneal fibrosis in rats, and its inhibitory effect is achieved by down-regulating the expression of TGF-β/Smad pathway.