Ameliorative Effect And Potential Mechanism Of Alpha-lipoic Acid On Peritoneal Fibrosis Induced By High Glucose Peritoneal Dialysis Solution In Rats

Objective:To investigate the ameliorative effect and mechanism of α-lipoic acid on peritoneal fibrosis induced by high glucose peritoneal dialysis solution in rats.Methods :Thirty SD rats were randomly divided into control group,model group,α-lipoic acid intraperitoneal injection high dose group(400 μmol/L),α-lipoic acid intraperitoneal injection medium dose group(300 μmol/L),α-lipoic acid intraperitoneal injection low dose group(200 μmol/L),α-lipoic acid gavage group(300 μmol/L),5 rats in each group.The rat model of peritoneal fibrosis was induced by intraperitoneal injection of 4.25%glucose peritoneal dialysis solution,and each group was administered separately at the corresponding dose starting on the day of modeling for 4weeks.The body weights of rats before and after modeling were recorded;The morphology of peritoneal tissues and peritoneal fibrosis were observed by HE and Masson’s staining;the expression of α-SMA and Collagen Ⅰ in peritoneal tissues was detected by immunohistochemical staining;the expression of TGF-β1,p-Smad 2 and p-Smad 3 proteins in peritoneal tissues was detected by Western blot.Results : No statistically significant differences of weight were found between the groups of rats before modeling and after treatment(P>0.05).Compared with the control group,the percentage of fibrosis expression area,α-SMA and Collagen Ⅰ expression in peritoneal tissue,and TGF-β1,pSmad 2 and p-Smad 3 protein expression in peritoneal tissue were significantly increased in the model group(P<0.01).Compared with the model group,the percentage of fibrosis expression area,peritoneal tissue α-SMA,Collagen Ⅰ expression,peritoneal tissue TGF-β1,p-Smad 2,p-Smad3 protein expression were significantly decreased in the α-lipoic acid intraperitoneal injection high dose group(P<0.05).The percentage of fibrosis expression area,peritoneal tissue α-SMA,Collagen Ⅰ expression,peritoneal tissue TGF-β1,p-Smad 2,and p-Smad 3 protein expression were significantly reduced in the α-lipoic acid intraperitoneal injection(high)dose group(P<0.05).Conclusion :α-Lipoic acid can alleviate peritoneal fibrosis induced by high glucose peritoneal dialysis fluid and inhibit TGF-β1/Smads signaling activation in rats,and the effect was stronger when administered intraperitoneally.