| With the development of modern society,chronic kidney disease has become a public health problem which affects millions of people worldwide.In recent years,its incidence is on the rise.The incidence of chronic kidney disease is about 10.8% in China,and there are about 130 million patients with chronic kidney disease.Patients with end-stage renal disease need renal replacement therapy.At present,the main renal replacement therapy includes hemodialysis,peritoneal dialysis and kidney transplantation.Peritoneal dialysis has been selected by more and more patients because of its advantages such as high early survival rate,good residual renal function protection,little influence on the cardiovascular system,and avoidance of repeated vascular puncture.Data from CNRDS,a Chinese research data service platform,shows that the number of peritoneal dialysis patients in 2019 was 103348,an increase of nearly twice as many as in 2012.Although peritoneal dialysis significantly improves the prognosis of patients with end-stage renal disease,there are still many complications that ultimately lead to the failure of peritoneal dialysis.The accumulation of glucose degradation products in the peritoneal dialysate triggers oxidative stress,which leads to the epithelial-mesenchymal transition of peritoneum,and peritoneal dysfunction will affect peritoneal ultrafiltration function.According to the regulations of the International Association of Peritoneal Dialysis,after leaving 2000 ml of 4.25% glucose dialysate in abdomen for 4 hours,the ultrafiltration volume less than 400 ml will be ultrafiltration failure.As a serious complication of long-term peritoneal dialysis,ultrafiltration failure has a negative impact on the survival of patients.However,there is few therapy to improve or treat ultrafiltration failure.Molecular hydrogen has good antioxidant stress and anti-inflammatory response ability.Diving medical research has proved that hydrogen at hundred times of therapeutic doses is also safe for the human body.It has been widely used in the treatment of a variety of diseases.Drinking hydrogen-rich water can alleviate oxalate-induced crystalline kidney damage.In the glucose-induced peritoneal fibrosis model,molecular hydrogen can effectively inhibit the transformation of peritoneal mesenchymal cells into mesenchymal cells,thus reducing the incidence of adverse events.This study will explore the effect of molecular hydrogen on peritoneal ultrafiltration function in peritoneal dialysis patients.Part One A retrospective study of dialysis adequacy and ultrafiltration function in single-center peritoneal dialysis patientsObjective:To study the changes of dialysis adequacy and peritoneal ultrafiltration function in single-center peritoneal dialysis patients.Methods:From August 1996 to March 2021,the continuous cases of peritoneal dialysis due to end-stage renal disease at Peritoneal Dialysis Center of Changhai Hospital were collected.The results of Kt/V,ultrafiltration volume and peritoneal balance test during the follow-up period of each patient were recorded.The survival status of each patient was recorded.According to age,sex and primary disease,these patients were divided into different groups.The dialysis adequacy and ultrafiltration function of the single-center peritoneal dialysis population were studied.The survival curve was plotted.Results:A total of 735 patients were select,including 412 males and 323 females,with an average age of 53.31±15.55 years.The average starting Kt/V was 2.2,1.8 for the 60 th month of dialysis,fluctuating between 1.7 and 2.1 after the 100 th month.The average initial ultrafiltration was +155 ml,rising to +800 ml at the 100 th month of dialysis,and the ultrafiltration volume gradually decreased after the 100 th month,the ultrafiltration volume was +570 ml at the 174 th month.D/Pcr fluctuated around 0.65 between the 0th and 150 th months of dialysis.The proportion of patients with high average transport and high transport in the initiation state of dialysis was 46.77%,the proportion of patients with high average transport and high transport in the 123 rd month of dialysis was 53.85%.After the 168 th month of dialysis,the proportion of patients with high average transport and high transport was 100%.The survival curves of the elderly,the male and the diabetic patients decreased more rapidly than other populations(P<0.05).Conclusion:With the extending time of dialysis,dialysis adequacy and ultrafiltration were decreased in every group.The elderly,the male and the diabetic groups were at higher risk.Part Two Effect of long-term hydrogen inhalation on ultrafiltration function of peritoneal dialysisObjective: To investigate the effect of long-term hydrogen inhalation on ultrafiltration function of peritoneal dialysis.Methods: Eligible peritoneal dialysis patients were admitted to hydrogen inhalation for a period of 6h/day for 1 year,with a flow rate of 300 ml/min and hydrogen integration of99.82%.These patients were given basic treatment at the same time.Comparing the changes of ultrafiltration volume before and after hydrogen aspiration.The changes of the concentrations of vascular endothelial growth factor A and platelet-derived growth factor BB in the outflow are also compared.Results: The median ultrafiltration volume increase after an average of 8.6 weeks of hydrogen aspiration in peritoneal dialysis patients was 80 ml.The median ultrafiltration volume increase after an average of 16.8 weeks of hydrogen aspiration in peritoneal dialysis patients was 125 ml.The median concentration of vascular endothelial growth factor A in peritoneal dialysis drainage was 383.90 pg/ml at beginning,down to 224.80 pg/ml after 8.6weeks of hydrogen inhalation,and 121.40 pg/ml after 16.8 weeks of hydrogen inhalation.The median concentration of platelet-derived growth factor BB in peritoneal dialysis drainage was 72.75 pg/ml at beginning,down to 40.90 pg/ml after 8.6 weeks of hydrogen inhalation,and 39.65 pg/ml after 16.8 weeks of hydrogen inhalation.Conclusion: Hydrogen can improve peritoneal ultrafiltration and reduce peritoneal angiogenesis.Part Three Experimental study on molecular hydrogen improving the ultrafiltration function of peritoneal dialysisObjective: To investigate the related mechanisms about hydrogen improving peritoneal ultrafiltration,providing a new target for the prevention and treatment of ultrafiltration failure.Methods: Twenty-four 7-week-old C57BL/6J mice were randomly divided into magnesium chloride group(magnesium ion control),high sugar + magnesium chloride group(model),high sugar + magnesium hydride group(treatment),and magnesium hydride group(normal control).4.25% high-glycemic peritoneal dialysate 2ml was intraperitoneal injected.183 mg/kg magnesium chloride solution 0.1 ml was gastric lavaged.50 mg/kg magnesium hydride suspension 0.1 ml was gastric filling(hydrogen production 2.125 ml).Each of the above had been carried out for 28 days,constructing a high-glucose induced model of peritoneal dialysis dysfunction.Pathological staining was performed to measure the subperitoneal mesothelial thickness of each group,and the Masson stained collagen volume integral was calculated.Assessing the peritoneal function by peritoneal reabsorption experiments.PTEN expression in peritoneum of mice detected by immunohistochemistry.Using bioinformatics analysis to explore the molecular mechanisms by which Lnc RNA GAS5 regulates on PTEN.Constructing stable overexpressed or knockdown of GAS 5 cell lines to verify the effects of Lnc RNA GAS 5 on PTEN and explore the possible mechanisms by which molecular hydrogen improves the ultrafiltration function of peritoneal dialysis.Results: After high glucose stimulation,the median subcutaneous thickness was 78.38 nm,while after molecular hydrogen intervention,the median subcutaneous thickness was23.03 nm.After high glucose stimulation,the median number of peritoneal collagen volume integrals was 41.6%,and after molecular hydrogen intervention,the median number of peritoneal collagen volume integrals was 20.0%.In the peritoneal reabsorption experiment,the reabsorption rate of the high glucose + magnesium chloride group was 76.00±21.10%,and the high glucose + magnesium hydride group was 91.50±2.30%.Under the stimulation of high glucose,the expression of peritoneal PTEN decreases,the expression of PTEN is adjusted after molecular hydrogen intervention,and gas5 and PTEN are changed in the same direction.GAS5 regulates the expression of PTEN on peritoneal tissue by competitively binding mi R-23a-3p.Conclusion: Hydrogen inhalation can alleviate high-glucose induced peritoneal fibrosis and improve peritoneal reabsorption.Molecular hydrogen can partially reverse the downregulation of PTEN stimulated by high glucose.This molecular phenomenon may be mediated by the ce RNA mechanism of GAS5/mi R-23a-3p/PTEN. |
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