Effect of ceramide on peritoneal mesothelial cells apoptosis induced by peritoneal dialysis solution / 中华肾脏病杂志

ABSTRACT

ObjectiveToexploretheeffectof ceremideonprocess of peritoneal mesothelial cells(PMCs) apoptosis induced by peritoneal dialysis solution(PDS).Methods PMCs were cultured with normal DMEM,1.5％ PDS and 4.25％ PDS.4.25％ mannitol was used as high osmotic pressure control.Ceremide were detected by LC-MS-MS.Flow cytometry was used in apoptosis analysis.Bax,p53 and bcl-2 protein expressions were detected by Western blotting.Results (1) PDS caused the increase of intracellular ceremide in PMCs,and normal and high osmotic pressure controls had no such effect.As the acidic sphigomyelinase inhibitor,desipramine significantly inhibited the production of ceramide induced by 4.25％ PDS [(56.08±12.24) μg/L vs (91.25t15.89) μg/L,P＜0.01]. (2) Compared with 1.5％ PDS,4.25％ PDS stimulated PMCs apoptosis (26.65％±6.21％ vs 4.04％±1.86％,P＜0.01),up-regulated bax and p53 proteins expression (P＜0.01),and down-regulated bcl-2 protein exprssion(P＜0.05).Desipramine obviously inhibited the apoptosis induced by 4.25％ PDS,decreased bax and p53 proteins expression,increased bcl-2 protein expression(P＜0.05).Exogenous C2-ceremide reversed the effect of desipramine(P＜0.05).Conclusion The increase of intracellular ceremide may play an important role in the PMCs apoptosis induced by high glucose PDS.