The Effect Of Icodextrin And Vitamin B₆ On The Mouse Peritoneum With High Concentration Of Peritoneal Dialysis Fluid

ObjectivePeritoneal dialysis is a recognized method of renal replacement therapy in the world.Peritonitis is previously the most common cause of peritoneal injury,as technology advances,increasingly reduced.But following longer time with peritoneal dialysis,the situation that peritoneal fibrosis inducing peritoneal ultrafiltration failure and exit from peritoneal dialysis becomes increasing.So how to block and slow down the process of peritoneal fibrosis,becomes a research hotspot.The main mechanism of peritoneal fibrosis is the long-term peritoneal exposure to non-physiological peritoneal dialysis solution,causes peritoneal mesothelial cells shedding,the accumulation of extracellular matrix,and ultimately the formation of peritoneal fibrosis,loss of ultrafiltration function.Advanced glycation end products are end products of protein,lipid,the part amino of nucleic acid and the aldehyde of reducing sugar occurs non-enzymatic oxidation of glycosylated.Its pathological mechanism in a variety of chronic diseases has been confirmed,in particular diabetes-related complications,in particular the fibrosis of organization playing an important role.The producing of AGEs is irreversible,dose and time-dependent.Research has shown that the deposition of AGEs in peritoneal with peritoneal dialysis patients after 3 months.Icodextrin is a glycan itself and could not take part in non-enzymatic glycosylation reaction,and its metabolic end products is maltose,it is difficult to participate in glycosylation reactions.Vitamin B₆ is a natural material,with anti-oxidation and has been proven to inhibit non-enzymatic glycosylation reaction and AGEs formation. Using this experiment observed the effect of high sugar and Icodextrin peritoneal dialysis fluid and vitamin B₆ on mouse peritoneal AGEs and RAGE,the impact of angiogenesis in mouse peritoneal perfusion model.Methods1.Animal origin:60 adult male Kunming mice weighing 18-25g of China Medical University animal experiment center.2.Peritoneal dialysis solution by intraperitoneal injection:2 times per day,1ml once.3.Experimental sub-groups:each group were given 4.25%peritoneal dialysis solution,4.25%peritoneal dialysis solution and 400mg/kg·d vitamin B₆,7.5% Icodextrin dialysis fluid,normal saline.4.Peritoneal vascular count,fluorescence detection of peritoneal AGEs,RT-PCR detected the expression of RAGE.ResultsAfter 6 weeks,the vascular density of high glucose group was higher than others (P＜0.05),the vascular density of Icodextrin group was higher than Vitamin B₆ group and control group,and have significant difference(P＜0.05).Vitamin B₆ group and control groups have no significant difference(P＞0.05).After 8 weeks,the vascular density of high glucose group was higher than others,and have significant difference(P＜0.05).The vascular density of high glucose group in 8 weeks was higher than in 6 weeks,and have significant difference(P＜0.05). The vascular density of Icodextrin group was higher than Vitamin B₆ group and control group,and have significant difference(P＜0.05).The vascular density of Vitamin B₆ group was higher than control group,and have significantly different(P＜0.05).Peritoneal AGEs fluorescence intensity of high glucose group(913.5±23.5)was significantly higher than the other three groups.Peritoneal AGEs fluorescence intensity of Vitamin B₆ group(479.6±43.2)was lower than high glucose group,but higher than control group(P＜0.05).Peritoneal AGEs fluorescence intensity of Icodextrin group (566.7±35.2)was lower than high glucose group,but higher than control group(P＜0.05).Peritoneal AGEs fluorescence intensity of Vitamin B₆ group was lower than Icodextrin group,and have significantly different(P＜0.05). High glucose peritoneal dialysis solution can enhanced RAGE expression,and has significantly different in semi-quantitative analysis(P＜0.01).RAGE expression of Vitamin B₆ group was lower than high glucose group,but higher than control group(P＜0.05).RAGE expression of Icodextrin group was lower than high glucose group,but higher than control group(P＜0.05).RAGE expression of Vitamin B₆ group was lower than Icodextrin group(P＜0.05).In this experiment,Peritoneal AGEs fluorescence intensity AGEs and semi-quantitative analysis of RAGE exists positive correlation.(P＜0.01,R²=0.97).ConclusionHigh glucose dialysis solution could increase mouse peritoneal AGEs,RAGE expression,and promote parietal peritoneum's angiogenesis.Icodextrin dialysis fluid could mildly increase mouse peritoneal AGEs,RAGE expression,and promote parietal peritoneum's angiogenesis,but the role of Icodextrin dialysis fluid is weaker than traditional high glucose dialysis solution.Vitamin B₆ could decrease mouse peritoneal AGEs,RAGE expression,and inhibit parietal peritoneum's angiogenesis,which induced by high glucose dialysis solution.To sum up,Icodextrin and vitamin B₆ dialysate have a protective effect on mice with peritoneal dialysis.