Effect of fosinopril on the expression of NADPH oxidase p22phox mRNA in the kidneys of diabetic rats / 中华肾脏病杂志

ABSTRACT

Objective To study the effect of fosinopril on the expression of NADPH oxidase subunit p22phox mRNA and the extracellular matrix (ECM) accumulation in the kidneys of rats with diabetes mellitus . Methods Diabetic rats induced by streptozotocin were randomly divided into control group(DM group) and fosinopril group (fosinopril 10 mg'kg-1·d-1) (DM+Fosin group) and treated for 12 weeks . Expression of p22phox mRNA of NADPH oxidase in kidneys was measured by RT-PCR . The expression of fibroneetin was studied by immunohistochemistry and matrix metalloproteinases 9 activity was detected by Zymography . Meanwhile, the kidney hypertrophy index, serum creatinine level and 24-hour urinary protein excretion were evaluated . Results The expression level of p22phox mRNA in the kidneys of DM+Fosin group rats was decreased by 45% than that of DM group at week 4 (P＜0 .05) . At week 8 fosinopril significantly decreased the expression of glomerular and tubulointerstitial fibronectin by 52,5% and 42 .9% respectively (P＜0 .05), while increased MMP-9 activity by 29 .6% (P＜0 .05) compared with DM group . Fosinopril significantly decreased 24-hour urinary protein excretion of diabetic rats from week 8 . Serum creatinine level, 24-hour urinary protein excretion and kidney hypertrophy index were significantly decreased by 35 .9%, 50 .2% and 17 .2% in rats of DM+Fosin group than those of DM group at week 12 (P＜0 .05) . Fosinopril did not affect blood sugar significantly . Conclusion Fosinopril has beneficial effect on diabetic nephropathy partly through inhibiting the expression of NADPH oxidase p22 phox mRNA .