Renal Protection Of Sulodexide And Its Mechanism In Diabetic Nephropathy

ObjectiveTo observe the efficacy and safety of sulodexide on patients of type2diabeticnephropathy who have received ACEI and/or ARB therapy.MethodsA total of92cases of type2diabetic nephropathy patients, who had received at leastone kind of ACEI and/or ARB drug therapy for at least6months, were devided into twogroups: the microalbuminuria group and the macroalbuminuria group. All the patients weregiven sulodexide60mg/d by intravenous infusion for10days, and then given sulodexide100mg/d by oral use for110days besides routine management. The blood pressure, fastingblood glucose, liver and kidney function, blood coagulation and24-hour urinary proteinwere measured before and4weeks,8weeks,12weeks and120days after the use ofsulodexide.ResultsThe24-hour urinary protein of the microalbuminuria group and the macroalbuminuriagroup were (0.62±0.13)g and (4.86±0.92)g before the treatment. And12weeks later, the24-hour urinary protein were （0.40±0.11）g and （3.02±0.73）g respectively. Thedifferences of the24-hour urinary protein before and after the treatment both of the groupswere significant（P<0.05）.120days of the treatment later, the24-hour urinary protein ofthe two groups were （0.36±0.12）g and （2.73±0.82）g, and reduced （38.97±14.67）%and （41.32±18.24）%respectively compared to those before the treatment. There wasno significant difference of the rate of the decline between the two groups（P>0.05）. There were no significant differences of the blood pressure, blood glucose, blood coagulation,liver and kidney function before and after the treatment both of the groups. There were noserious adverse events occurred during the treatment.ConclusionsSulodexide can effectively reduce urinary protein of type2DN patients withmicroalbuminuria or macroalbuminuria who have received ACEI and/or ARB therapy. Ithad no significant effect on the blood pressure, blood glucose, blood coagulation, liver andkidney function in short term. And it’s safe in clinical application. ObjectiveTo observe the renal protection of sulodexide in diabetic rats and to investigate themechanism.MethodsThe rat models of type1diabetes were established by intraperitoneal injection of STZ(streptozotocin,60mg/kg). Then the rats were randomly devided into four groups: DMgroup (diabetic model group), S10group (10mg/kg/d sulodexide group), S20group(20mg/kg/d sulodexide group), L group (losartan30mg/kg/d group),10rats per group.Another10normal rats were used as N group (normal control group). All the rats weretreated for12weaks. Then body weight,24-hour urinary albumin excretion, blood glucose(BG),serum creatinine(Scr), blood urea nitrogen(BUN) and kidney weight were measured;renal tissue samples were observed under optical and electron microscope. Expressions ofVEGF, VEGF receptor2(VEGF-R2), SOCS1and TGF-β1in renal tissue samples weredetected by Western blotting and immunohistochemistry.ResultsCompared with N group, DM group had significantly higher24-hour urinary albuminexcretion, Scr and BUN (P＜0.01), the pathological changes in the renal tissue samples inDM group were also obvious. Compared with DM group, the treated groups (S10, S20, and L group) had significantly lower24-hour urinary albumin excretion（P<0.05or P<0.01）,but there were no significant differences of Scr and BUN among the treated groups andDM group（P>0.05）. Compared with S10group, S20and L group had significantly lower24-hour urinary albumin excretion（P<0.05）. The pathological changes in the renal tissuesamples were much ameliorated in the treated groups, especially those in the S20and Lgroup. The expressions of VEGF and VEGF-R2in DM group were significantly higherthan those in N group （P<0.01）, and the expressions in the treated groups weresignificantly lower than that in DM group（P<0.05or P<0.01）. The expression of SOCS1in DM group was significantly higher than that in N group （P<0.05）, and the expressionin the treated groups was much higher than that in DM group （P<0.05or P<0.01）. Theexpression of TGF-β1in DM group was significantly higher than that in N group（P<0.01）,and the expression in the treated groups was significantly lower than that in DM group（P<0.05or P<0.01）.ConclusionsSulodexide has renal protective effect in diabetic rats, and20mg/kg/d is moreeffective than10mg/kg/d. The nephroprotective effect may be related to the regulating ofthe expressions of VEGF, VEGF-R2, SOCS1and TGF-β1in the renal tissues of diabeticrats.