Effect of sulodexide on podocalyxin expression of podocytes in streptozotocin diabetic desoxycorticosterone acetate-hypertensive rats / 中华肾脏病杂志

ABSTRACT

Objective To explore the effect of suledexide on renal injury and podocalyxin expression of podocytes in STZ diabetic desoxycorticosterone acetate (DOCA)-hypertensive rats. Methods Wistar rats were subjected to subcutaneous injection of streptozotocin(STZ), followed by uninephrectomy and subcutaneous administration of DOCA. Diabetic and hypertensive rats were randomly allocated to treatment with sulodexide or a combination of sulodexide and telmisartan for 8 weeks. Blood pressure (BP), 24-hour urinary albumin were measured every 2 weeks. Blood and urinary samples were collected to detect biochemical indexes of plasma and urinary β-acetyl-β-D-glucosaminidase (NAG) at the end of the study. Immunohistochemistry (IHC), RT-PCR and Western blot were performed to examine the expression and distribution of podocalyxin. Results STZ +DOCA-treated rats progressively developed hypertension, albuminuria and hyperglycemia. Hyperlipidemia and hypoinsulinemia were found in diabetic and hypertensive rats compared with controls. Albuminuia was significantly reduced in sulodexide group at week 8 and sulodexide plus telmisartan group at week 6 and week 8. Blood pressure decreased in sulodexide plus telmisartan group. No significant effects on lipid and glucose metabolism were observed in all treated groups. Histopathological index increased in STZ+DOCA-treated rats, but was significantly lower in sulodexide group as well as sulodexide plus telmisartan group. The number of podocytes on glomerular cross-section of the four groups were comparable. Segmental loss and down-regulation of podocalyxin were detected in STZ+DOCA-treated rats, which were greatly attenuated by sulodexinde, meanwhile, combination treatment preserved more podocalyxin expression in glomeruli than sulodexide monotherapy. Conclusion Sulodexide effectively reduces albuminuria, prevents loss of podocyte podocalyxin and alleviates renal damage in STZ diabetic DOCA-hypertensive rats.