Effect Of Low Molecular Weight Heparin On Proteinuria In Rats With Nephrotic Syndrome And Its Mechanism

Objective:Observe the effect of low molecular weight heparin(LMWH)on proteinuria in rats with nephrotic syndrome(NS)and explore the role of Glycocalyx(GCX)in the formation of proteinuria in NS rats.Methods:Thirty 8-week-old male SD rats were randomly divided into 5 groups: control group,model group,and groups treated with LMWH for 5 d,7 d and 9 d(Treat1,Treat2,Treat3).All the rats were injected with adriamycin into the tail vein to make NS model except the rats in control group.Each treatment groups was given subcutaneous injection of LMWH for 5 d,7 d and 9 d after the successful establishment of the model.Collecting 24 hours’ Urine after administration and detecting the urine protein content,and plasma heparin sulfate(HS),heparanase(HPSE),Syndecan-1,TNF-α,IL-6,serum total cholesterol and serum albumin were detected by Elisa kit.The contents of GCX core protein Glypican-1 and Syndecan-1 in renal cortex of rats were detected by Western blot,and the pathological changes of renal tissues after LMWH treatment were observed by HE staining.The thickness of GCX on rat glomerular endothelial cells was observed by transmission electron microscopy.Result:Compared with the model group,the plasma HS content in the LMWH group was lower(P < 0.05)but Syndecan-1 was higher.the Syndecan-1 decreased on the 9th day(P > 0.05);The levels of plasma TNF-α and IL-6 were significantly lower than those of the model group(P < 0.05),but there was no significant difference between the treatment groups.;The results of WB showed that the contents of Glypican-1 and Syndecan-1 in the renal cortex were higher than those in the model group,and the results of HE staining showed that the type of clear tubules in the renal tubules was significantly decreased in the LMWH treatment groups.The results of transmission electron microscopy showed that the thickness of glucose calyx on the surface of glomerular endothelial cells in the model group was significantly lower than that in the normal control group,and it was significantly thickened after LMWH treatment.Conclusion:LMWH can reduce the exfoliation of glomerular endothelial calyx,protect endothelial calyxand decrease the content of TNF-α and IL-6 in serum of rats with nephrotic syndrome.Reducing urinary protein content and promoting plasma albumin may be one of the protective mechanisms of NS kidney.