| Objective Peritoneal Dialysis(Peritoneal Dialysis, PD) is an effective treatment for end-stage renal disease ESRD, but the long-term peritoneal dialysis peritoneal fibrosis may occur, resulting in the loss of structure and function of the peritoneum, the peritoneal fibrosis ultimately lead to failure of peritoneal ultrafiltration which is the main reason of dropping out of treatment for the peritoneal dialysis patients.Prevention and delay of peritoneal fibrosis are the key to ensuring long-term success for the peritoneal dialysis patients.Melatonin,the main hormone secreted by the pineal body,has anti-inflammatory, antioxidant, anti-fibrosis effects; pirfenidone(pirfenidone, PFD)is a novel broad-spectrum anti-fibrotic drug,with which renal fibrosis, liver fibrosis model exhibited significant anti-fibrotic effects. Melatonin and pirfenidone have not been used in peritoneal dialysis-related prevention and treatment of peritoneal fibrosis.In this study, high glucose peritoneal fibrosis was induced by intraperitoneal injection and the rats were given melatonin and pirfenidone intervention.We can observe their peritoneal dialysis impact-related peritoneal fibrosis,hoping it to provide new ideas on peritoneal dialysis-related prevention and treatment.Methods 46 male SD rats were randomly divided into six groups.(1) control group(n =6): intraperitoneal injection of ethanol within 0.9% saline 20 ml + treatment with equal volume of triple-distilled water diluted;(2) the model group(n = 8): Intraperitoneal injection with 4.25% peritoneal dialysis fluid by body weight daily 100 ml / kg + 0.9%of NS with an equal volume of therapy;(3) low-dose melatonin group(n = 8):Intraperitoneal injection with 4.25% peritoneal dialysis fluid by body weight daily100 ml / kg + melatonin by 5mg / kg;(4) the dose of melatonin group(n = 8):Intraperitoneal injection with 4.25% peritoneal dialysis fluid by body weight daily100 ml / kg + melatonin by 10 mg / kg;(5) high-dose melatonin group(n = 8):Intraperitoneal injection with 4.25% peritoneal dialysis fluid by body weight daily100 ml / kg + melatonin by 20 mg / kg;(6)pirfenidone group(n = 8): Intraperitoneal injection with 4.25% peritoneal dialysis fluid by body weight daily 100 ml / kg +administered by stomach tube with pirfenidone by 500 mg / kg. After 28 days the experiment rats were sacrificed.The following indicators need to be measured:4 hours peritoneal equilibration test(PET), amount of ultrafiltration(UF), blood and peritoneal fluid specimens dialysate urea nitrogen concentration(D), plasma urea nitrogen concentration(Purea), initial dialysate glucose concentration(D0), dialysate glucose concentration(D4), and calculate the D / Purea, D4 / D0. Rats were killed,taking the parietal and visceral peritoneum HE and Masson staining to observe the morphological changes of the peritoneum. We use immunohistochemical methods to detect visceral peritoneum of transforming growth factor β1(TGF-β1), collagen I(Col-I) and α-smooth muscle actin(α-SMA) expression.Results The results showed that :1.Four hours equilibrium experiments of the peritoneal dialysis showed that, to be compared with the normal group, UF(ultrafiltration) and D4/ D0(4 hours after the dialysate glucose concentration / initial dialysate glucose concentration) of the model group decreased, P <0.05, the difference was statistically significant, D / Purea(dialysate urea nitrogen concentration / plasma urea nitrogen concentration) increased, P <0.05, the difference was statistically significant; high,medium and low-dose melatonin groups were in comparation with model group, the result showed that UF(ultrafiltration) and D4 / D0(4 hours after the dialysate glucose concentration / initial dialysate glucose concentration) increased, P<0.05, the differencewas statistically significant, D / Purea(dialysate urea nitrogen concentration / plasma urea nitrogen concentration) decreased, P<0.05, the difference was statistically significant; pirfenidone group was compared with the model group, the result showed that the difference was not statistically significant; pirfenidone group was in comparation with the high, medium and low-dose melatonin group, the result showed that UF(ultrafiltration) and D4 / D0(4 hours after revealing Liquid glucose concentration / initial dialysate glucose concentration) decreased, P> 0.05, the difference was not statistically significant, D / Purea(dialysate urea nitrogen concentration / plasma urea nitrogen concentration) increasesd, P> 0.05, the difference was not statistically significant; 2,HE and Masson staining showed that the peritoneal of the control group was thin and smoothy, the peritoneum of the model group was thickened, the visible part of mesothelial cells shedding skin visible between stromal was thickening and vascular proliferation of the melatonin groups in comparation with the above peritoneal pathology model group was significantly reduced, the high-dose group was significantly reduced in comparation with the low-dose group in lesions;these pathological changes of the pirfenidone group had no significant change in comparation with the model group; 3, Immunohistochemistry showed: TGF-β1, Col-I,α-SMA in control rats were almost not expressed, the model group expressed the most,,TGF-β1, Col-I, α-SMA expression of the model group increased in comparation with the control group, P<0.05, the difference was statistically significant; TGF-β1, Col-I,α-SMA expression of the high, medium and low-dose melatonin groups was decreased in comparation with the model group, P<0.05, the difference was statistically significant;the difference between the pirfenidone group and model group ratio was not statistically significant;TGF-β1, Col-I, α-SMA expression of the high-dose group decreased in comparation with the low-dose melatonin group, P <0.05, the difference was statistically significant; the pirfenidone group was compared with high, medium and low-dose melatonin groups, the result showed that TGF-β1, Col-I, α-SMAexpression increased, P> 0.05, the difference was not statistically significant.Conclusions 1.This experiment successfully replicated peritoneal fibrosis in rats;2.Melatonin can inhibit peritoneal fibrosis in rats by improving the structure and function of the peritoneum;3.The antifibrotic function of melatonin may be related to the reduction of expressions of the TGF-β1, α-SMA and the suppression of the synthesis of Col-I;4.Pirfenidone can not inhibit peritoneal fibrosis in rats. |
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