Curcumin Regulates Autophagy To Improve High Glucose-induced Peritoneal Fibrosis

Objective: In peritoneal dialysis,glucose is still the standard and most widely used penetrant in peritoneal dialysate.Long-term peritoneal dialysis,peritoneal exposure to high-sugar peritoneal dialysate,can cause peritoneal structure and dysfunction,causing peritoneal fibrosis,ultrafiltration failure,is an important reason for uremia patients to withdraw from peritoneal dialysis.High glucose can inhibit the occurrence of peritoneal fibrosis by inhibiting autophagy pathway.Therefore,autophagy pathway can be used as a potential new target for the treatment of peritoneal fibrosis.As a traditional Chinese medicine preparation,curcumin has broad clinical application prospects in anti-fibrosis because of its non-toxic,small side effects and multi-target,multi-channel and multi-link functions.Therefore,we explored the protective effect of curcumin on autophagy in high glucose-induced peritoneal mesothelial cell fibrosis,and provided new ideas for prevention and treatment of peritoneal dialysis-related peritoneal fibrosis.Methods: 1.Human peritoneal mesothelial cells were cultured in vitro,and the mammalian rapamycin target protein(m-TOR)inhibitor rapamycin(R)was pre-stimulated for one hour at 10 nmol/l,and then in a high glucose environment for 24 hours.The peritoneal mesothelial cells were divided into three groups: normal control group(L,25 mmol/l),high glucose group(G,126 mmol/l),high glucose group +rapamycin group(GR,G126 mmol/l+R10nmol/l).Western blot was used to detect the expression of fibrosis markers E-cadherin,α-SMA and autophagy markers LC3II/I and Beclin-1.2.The survival rate of human peritoneal mesothelial cells were detected by MTT method.The curcumin(C)stimulation concentration range was 0-10umol/L.The peritoneal mesothelial cells were grouped and given curcumin(1,5,10 umol/l)pre-stimulated for 1 h and then incubated for 24 hours in a high sugar environment.A total of five groups: control group(L,25 mmol / l),high sugar group(G,126 mmol / l),high sugar + curcumin 1umol / l(GC1,G126 mmol / l + C1 umol / l),high sugar +turmeric 5umol / l(GC5,G126 mmol / l + C5 umol / l),high sugar + curcumin 10 umol / l(GC10,G126 mmol / l + C10 umol / l).Western blot was used to detect the expression of fibrosis markers E-cadherin,α-SMA and autophagy markers LC3II/I and Beclin-1.Results: 1.High glucose can reduce the occurrence of peritoneal fibrosis caused by autophagy Western blot analysis showed that compared with the control group,the expression of E-cadherin(P<0.05)and the expression of α-SMA(P<0.05)were increased in the high glucose group,with the ratio of LC3II/I(P<0.05)and the expression of Beclin-1(P<0.05)was significantly reduced.Compared with the high sugar group,the expression of LC3II/Iand Beclin-1 was increased in the rapamycin group,and the expression of E-cadherin was increased and the expression of α-SMA was decreased(P<0.05).2.Curcumin reverses autophagy in a dose-dependent manner to attenuate the occurrence of peritoneal fibrosis caused by high glucose Western blot analysis showed that compared with the high glucose group,the expression of E-cadherin(P<0.05)was up-regulated and the expression of α-SMA(P<0.05)was down-regulated,the ratio of LC3II/I(P<0.05)and Beclin.-1 expression was up-regulated(P < 0.05).Conclusions: High glucose can induce peritoneal fibrosis by inhibiting autophagy;curcumin upregulates autophagy to improve high glucose-induced peritoneal fibrosis,and it is concentration-dependent in a certain range(0-10ummol/l).