Effect Of Sulodexide On TGF-β1/Smad、KLF10and KLF15of Long-term Peritoneal Dialysis Rats

ObjectiveTo investigate the effect of sulodexide on the mechanism of peritoneal fibrosisaction of long-term peritoneal dialysis rats.MethodsTwenty-six SD rats were randomly divided into three groups: control group （n=6）received no treatment; model group （n=10） received20mL4.25%peritoneal dialysisfluid daily IP for8weeks; SLX group （n=10） received20mL4.25%peritoneal dialysisfluid plus20mg·kg^-1·BW SLX daily IP for8weeks. Except for control group,peritoneal catheters were implanted in other twenty rats. At the end of the study, all therats were humanely killed. The parietal peritoneum tissues of rats were harvested andstained by hematoxylin-eosin and Masson trichrome. The morphology changes ofpartial peritoneum were examined by light microscopy Mesenteric expression ofSmad2、Smad3、Smad7、KLF10and KLF15mRNA were evaluated by RT-PCR.Theexpression of TGFβ1and α-SMA in parietal peritoneum were detected withimmunohistochemistry assay and p-Smad2/3、 Smad7、 KLF10、 KLF15proteinexpression were evaluated by Western BlotResults1.Six rats were excluded from further analysis because of clogging of the catheteror peritonitis. There were no differences in body weight （P＞0.05）.2.Compared with control group, the number of peritoneal vessels, inflammatorycells, and peritoneal thickness were significantly increased （P＜0.05）.Additional use ofsulodexide decreased the number of peritoneal vessels, inflammatory cells andperitoneal thickness（P<0.05）.3.Compared with control group, Smad2、Smad3、Smad7、KLF10mRNA levels and the expression of protein in TGFβ1、α-SMA、p-Smad2/3、Smad7、KLF10inperitoneum were significantly increased meanwhile KLF15was significantlydecreased in model group（P＜0.05）. Up-regulation of the expression of Smad2、Smad3、Smad7、KLF10in mRNA and TGFβ1、α-SMA、p-Smad2/3、Smad7、KLF10in protein in peritoneum were suppressed by SLX. In the meantime, the expression ofKLF15in peritoneum was increased by SLX （P＜0.05）.Conclusions1. A type of peritoneal fibrosis model in rat was successfully established.2. SLX could improve peritoneal fibrosis through down-regulation of TGFβ1、p-Smad2/3、Smad7、KLF10and up-regulation of KLF15. Down-regulation KLF10andup-regulation of KLF15can indirectely influence the expression of Smad.