Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
J Diabetes Res. 2013;2013:134395. doi: 10.1155/2013/134395. Epub 2013 Jul 15.
Adrenomedullin has an antioxidative action and protects organs in various diseases. To clarify the role of adrenomedullin in diabetic nephropathy, we investigated the NADPH oxidase expression, renin-secreting granular cell (GC) hyperplasia, and glomerular matrix expansion in the streptozotocin (STZ)-induced diabetic adrenomedullin gene knockout (AMKO) mice compared with the STZ-diabetic wild mice at 10 weeks. The NADPH oxidase p47phox expression and lipid peroxidation products were enhanced in the glomeruli of the diabetic mice compared with that observed in the controls in both wild and AMKO mice. These changes were more obvious in the AMKO mice than in the wild mice. Glomerular mesangial matrix expansion was more severe in the diabetic AMKO mice than in the diabetic wild mice and exhibited a positive correlation with the degree of lipid peroxidation products in the glomeruli. Proteinuria was significantly higher in the diabetic AMKO mice than in the diabetic wild mice. The GC hyperplasia score and the renal prorenin expression were significantly increased in the diabetic AMKO mice than in the diabetic wild mice, and a positive correlation was observed with the NADPH oxidase expression in the macula densa. The endogenous adrenomedullin gene exhibits an antioxidant action via the inhibition of NADPH oxidase probably by suppressing the local renin-angiotensin system.
肾上腺髓质素具有抗氧化作用，可以保护各种疾病中的器官。为了阐明肾上腺髓质素在糖尿病肾病中的作用，我们研究了链脲佐菌素（STZ）诱导的糖尿病肾上腺髓质素基因敲除（AMKO）小鼠与 STZ 诱导的野生型糖尿病小鼠相比，在 10 周时 NADPH 氧化酶表达、肾素分泌颗粒细胞（GC）增生和肾小球基质扩张的情况。与野生型小鼠相比，糖尿病小鼠的肾小球 NADPH 氧化酶 p47phox 表达和脂质过氧化产物增强。这些变化在 AMKO 小鼠中比在野生型小鼠中更为明显。糖尿病 AMKO 小鼠的肾小球系膜基质扩张比糖尿病野生型小鼠更为严重，并且与肾小球中脂质过氧化产物的程度呈正相关。糖尿病 AMKO 小鼠的蛋白尿明显高于糖尿病野生型小鼠。糖尿病 AMKO 小鼠的 GC 增生评分和肾原肾素表达明显高于糖尿病野生型小鼠，并且与致密斑 NADPH 氧化酶表达呈正相关。内源性肾上腺髓质素基因可能通过抑制局部肾素-血管紧张素系统来发挥抗氧化作用，从而抑制 NADPH 氧化酶。
