Curcumin regulated TGF-β1/Smad signaling pathway for improving peritoneal fibrosis related to peritoneal dialysis in rats and understanding its mechanism

Objective To explore the effect of curcumin on peritoneal fibrosis(PF) associated with peritoneal dialysis(PD) in rats and elucidate its possible mechanism.Methods Ten male Wistar rats were selected as normal group(normal saline) while the remaining rats were randomly divided into model group(normal saline), curcumin low-dose(15 mg·kg^-1·d^-1), medium-dose(30 mg·kg^-1·d^-1) and high-dose(60 mg·kg^-1·d^-1) groups(n=10 each).At the same time, 4.25% glucose PD solution(100 mL/kg) was intraperitoneally injected for 30 consecutive days.And 4h peritoneal balance test was performed for evaluating peritoneal function.Peritoneal thickness was measured.Hematoxylin-eosin(HE) and Masson stains were performed for observing the pathological changes of peritoneum.The levels of tumor necrosis factor-α(TNF-α), interleukin 6(IL-6) and interleukin 1β(IL-1β) in peritoneal tissue were determined by enzyme-linked immunosorbent assay(ELISA).Western blot was employed for detecting the relative expressions of transforming growth factor -β1(TGF-β1), Smad2/3, p-Smad2/3, Smad7, α-smooth muscle actin(α-SMA) and type Ⅰ collagen(Col Ⅰ) proteins in peritoneal tissues.Results As compared with normal group, peritoneal ultrafiltration volume(UFV) of model group declined, glucose transfer volume(MTG) expanded and peritoneal thickness increased(P<0.05).There were structural disarray, deformation of mesenchymal cell, infiltration of inflammatory cell and collagen deposition.In peritoneal tissues, the levels of TNF-α, IL-6 and IL-1β spiked, the relative expression levels of TGF-β1, p-Smad2/3, α-SMA and Col Ⅰ protein jumped and the relative expression level of Smad7 white declined(P<0.05).As compared with model group, peritoneal tissue UFV rose, MTG and peritoneal thickness declined(P<0.05) and structure grew gradually more intact, inflammatory infiltration and collagen deposition declined in curcumin low/medium/high-dose group.The levels of TNF-α, IL-6 and IL-1β declined, the relative expression levels of TGF-β1, p-Smad2/3, α-SMA and Col Ⅰdropped and the relative expression level of Smad7 white rose(P<0.05).The effect of curcumin on PD-related PF rats was dose-dependent.Conclusions Curcumin could alleviate peritoneal histopathological injury and improve peritoneal dysfunction in PD-related PF rats, and its mechanism may be related to alleviating inflammatory response, blocking the activation of TGF-β1/Smad signaling pathway, and then inhibiting the occurrence and development of PF.