Effect of different doses of rAAV-AS on the renal function in rats with diabetic nephropathy

Objective To investigate the effect of different doses of recombinant adeno-associated virus carrying human angiostatin gene(rAAV-AS) on the renal function in rats with diabetic nephropathy.Methods 10 out of 60 male SD rats of clean grade were randomly allotted as the normal control group,while the others were used to establish models of diabetic rats.Streptozotocin(STZ) 60 mg/kg was intraperitoneally injected in rats at the end of 12 h of fasting to induce diabetic model.72 h later,the blood glucose level of caudal vein was above 16.7 mmol/L,and the diabetic model was marked as successful.After a week of adaptation,diabetic rats were randomized into 5 groups(n=10): group DN,group rAAV-0,group AS1(1×1012 VG/kg),group AS2(2×1012 VG/kg),group AS3(4×1012 VG/kg).Different doses of rAAV-AS were injected into groups AS1,AS2 and AS3 from the caudal vein,and the corresponding doses of normal saline were injected in group NC and corresponding doses of rAAV-0 idler injected in group DN.At the end of the 8th weeks,their body weight(BW) and kidney weight(KW) were measured to calculate kidney index(KI).The blood glucose(BG),glycosylated hemoglobin(HbA1c),miscroalbunminuria(MAU),blood urea nitrogen(BUN) and serum creatinine(SCr) were determined.Results Compared with group NC,the levels of KI,BG,HbA1c,MAU,BUN and SCr increased significantly in DN,rAAV-0 and AS1 groups(P0.05).Compared with group DN,the levels of KI,MAU,BUN and SCr significantly decreased in groups AS2 and AS3(P0.05).Compared with group rAAV-0,the levels of KI,MAU,BUN and SCr significantly decreased in groups AS2 and AS3(P0.05).Compared with group AS1,the levels of KI,MAU,BUN and SCr significantly decreased in groups AS2 and AS3(P0.05).Conclusions rAAV-AS of medium and large doses has protective effect on the kidneys in diabetic rats,independent of the decrease of blood glucose level.