Effects of irbesartan on expression of integrin-linked kinase and podocyte injury in rats with early diabetic nephropathy

AIM: To determine the influence of irbesartan (Irb) on the podocyte injury and of integrin-linked kinase (ILK) expression in early experimental diabetic nephropathy (DN).METHODS: The hyperglycemic DN rat model was induced by intraperitoneal injection of streptozotocin (STZ,35 mg/kg) in spontaneously hypertensive rats (SHR).The diabetic SHR were randomly divided into 2 groups: DN SHR (DN,n=8) and DN SHR treated with irbesartan (50 mg/kg per day by gavage for 8 weeks,DN+Irb,n=9).Non-diabetic normotensive Wistar-Kyoto rats (WKY,the animals of normal blood pressure have the same genetic background with SHR) were used as control (control,n=11).The biochemical parameters and pathological changes were analyzed.Moreover,the influence of irbesartan on the expression of ILK and podocyte injury in SHR with DN was examined.RESULTS: Compared with control,DN SHR were associated with hyperglycaemia,hypertension,hyperlipidaemia,insulin resistance and albuminuria,which were similar to those of human T2DN.In addition,these DN SHR showed expansion of mesangial matrix,loss of podocyte and podocyte injury.Importantly,the expression of ILK in DN SHR was upregulated as compared to control.Treatment with irbesartan significantly decreased this overexpression of ILK,along with a decrease in albuminuria,reduction of blood pressure,prevention of podocyte injury,inhibition of mesangial matrix expansion and restoration of podocyte numbers.CONCLUSION: ILK is involved in the podocyte injury in DN.Irbesartan downregulates the expression of ILK and decreases podocyte injury.