Effect of high glucose-based peritoneal dialysis fluids on NLRP3-IL-1β in human peritoneal mesothelial cells / 北京大学学报(医学版)

Objective:To explore the effect of high glucose-based peritoneal dialysis fluids on NLRP3-IL-1β in human peritoneal mesothelial cells.Methods:HMrSV5 cells (SV40 immortalized human peritoneal mesothelial cell line) were grown in type Ⅰ collagen-coated dishes in DMEM/F12 containing 10％ fetal calf serum (FCS).All experiments on HMrSV5 cells were performed between passages 5 and 10.The cells were divided into 7 groups:control,1.5％ dextrose,2.5％ dextrose,4.25％ dextrose,rotenone,thenoyltrifluoroacetone (TTFA),and antimycin A.Immunoblotting was used to evaluate the expression of IL-1 β.Small interfering RNA (siRNA) targeting NLRP3 was used to downregulate the expression of NLRP3 and Western blot was used to evaluate the expression of IL-1 β in human peritoneal mesothelial cells exposed to 4.25％ dextrose.In the meanwhile,resveratrol (RSV) was used to induce autophagy,3-methyladenine (3-MA) and siRNA against Beclin 1 or ATG5 were used to block autophagy,flow cytometric was used to analyze the respiring (mitotracker deep red),total (mitotracker green) and reactive oxygen species (ROS)-generating mitochondria (mitoSOX);Western blot was used to evaluate the expression of IL-1β.Results:The IL-1β relative expressions were 0,0.175 ±0.082,0.418 ± 0.163,2.357 ±0.288,2.642 ±0.358,3.271 ±0.462,and 0.123 ±0.091,indicating that the cells exposed to high glucose-based peritoneal dialysis fluids and cells treated with mitochondria respiratory chain key enzyme complex Ⅰ,and complex Ⅲ inhibitors increased the IL-1β expression.And we found that NLRP3 knock-down significantly blocked the upregulation of IL-1 β.In addition,the fluorescence intensity of total mitochondria and ROS-generating mitochondria in the following groups:control,negative control,RSV,3-MA,ATG5 siRNA,Beclin1 siRNA were 1.76 ± 0.42,1.83 ± 0.55,1.85 ± 0.62,7.36 ± 0.92,5.35 ± 0.77,5.06 ± 0.62 and 821.68 ± 95.12,868.15 ± 102.82,723.39 ± 92.56,1 660.08 ± 113.65,1 433.01 ± 107.24,1 562.36 ± 112.88 respectively.The increased concentrations of mitochondrial ROS and IL-1β upregulation were confirmed in the inhibition but not the induction of autophagy.We also found that downregulation of ATG5 and Beclin1 sensitized cells for the release of IL-1β induced by MSU (monosodium urate) or nigericin which was the NLRP3 inflammasome activator.RSV treatment attentuated this effect.Conclusion:Long-term application of high glucose-based peritoneal dialysis fluids can trigger the consistent activation of NLRP3-IL-1ββ in peritoneal mesothelial cells.Timely initiation of autophagy may block the NLRP3-IL-1ββ activation and provide a basis for the further development of a potential therapeutic strategy for delay of chronic inflammation and peritoneal fibrosis associated with peritoneal dialysis.

Protective measures against ultrafiltration failure in peritoneal dialysis patients

Ultrafiltration failure in patients undergoing peritoneal dialysis is a condition with an incidence that increases over time. It is related to increased cardiovascular morbidity and mortality and is a major cause of the abandonment of the treatment technique. Because the number of patients undergoing renal replacement therapy is increasing with society aging and because approximately 10 percent of this population is treated with peritoneal dialysis, this matter is becoming more common in everyday practice for clinicians involved in the care of patients with chronic renal failure. In this review, we summarize the available measures used to prevent and treat ultrafiltration failure and the current state of research in the field, both in the experimental and clinical settings, focusing on the possible clinical applications of recent findings.

The latest development of two-compartment peritoneal dialysis fluids with low glucose degradation products / 医学研究生学报

The biological incompatibility of traditional peritoneal dialysis fluids(PDF) is the main reason for the poor outcomes of long-term peritoneal dialysis and the high rate of technical failure.Recently,two-compartment PDF has been applied in the treatment of peritoneal dialysis patients,and reportedly has lots of clinical advantages due to its better biocompatibility.This paper presents an overview of recent advances in the studies of two-compartment PDF.