福辛普利对糖尿病大鼠肾脏NADPH氧化酶p22phox亚基mRNA表达的影响

目的 观察福辛普利对链脲佐菌素(STZ)诱导的糖尿病大鼠肾脏还原型辅酶Ⅱ(NADPH)氧化酶p22phox 亚基mRNA表达及细胞外基质（ECM）聚积的影响，并探讨其可能机制。 方法 STZ诱导的糖尿病大鼠模型，随机分为糖尿病非治疗组（DM组）和福辛普利治疗组（DM+Fosin组，福辛普利10 mg·kg-1·d-1），疗程12周。RT-PCR法检测肾脏NADPH氧化酶p22phox mRNA的表达；免疫组织化学方法检测肾脏纤连蛋白（FN）表达；白明胶酶谱法检测肾脏基质金属蛋白酶9（MMP-9）的活性；并检测Scr、尿蛋白排泄量和肾质量指数等指标。 结果 实验第4 周，DM+Fosin组大鼠肾脏NADPH氧化酶p22phox mRNA表达较DM组减少45％（P ＜ 0.05）。第8周时，DM+Fosin组的肾小球和肾小管间质FN表达较DM组分别降低52.5％和42.9％（均P ＜ 0.05）；肾脏MMP-9的活性升高29.6％（P ＜ 0.05）。实验第12周时，DM+Fosin组大鼠Scr水平、尿蛋白量（24 h）和肾质量指数较DM组分别降低35.9％、50.2％和17.2％（均P ＜ 0.05）。DM+Fosin组和DM组血糖的差异无统计学意义（P ＞ 0.05）。 结论 福辛普利可延缓糖尿病肾病的发生和发展，其机制可能与通过抑制NADPH氧化酶p22phox亚基mRNA的表达有关。

Effect of fosinopril on the expression of NADPH oxidase p22phox mRNA in the kidneys of diabetic rats

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 .