Arginine reduces kidney collagen accumulation, cross-linking, lipid peroxidation, glycoxidation, kidney weight and albuminuria in the diabetic kk mouse

Arginine reduces kidney collagen accumulation, cross-linking, lipid peroxidation, glycoxidation, kidney weight and albuminuria in the diabetic kk mouse
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DOI:
10.1159/000189534
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发表时间:
1997-02-01
期刊:
影响因子:
2.5
通讯作者:
Hoger, H
Hoger, H
中科院分区:
医学4区
文献类型:
--
作者:
Lubec, B;Aufricht, C;Hoger, H

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在糖尿病肾病中,目前的主要发病机制是通过增加胶原合成和减少降解而增加肾小球中的胶原积累。在本研究中,我们测试了精氨酸是否能够影响糖尿病kk小鼠肾脏脂质过氧化、糖基氧化、胶原积累、葡萄糖介导的交联、羟基自由基攻击、蛋白质氧化、一氧化氮形成和蛋白尿的假设。10只糖尿病kk小鼠给予精氨酸50 mg/kg体重,10只糖尿病kk小鼠不治疗并作为阴性对照,10只kk小鼠作为健康对照。我们的研究结果表明,口服低剂量精氨酸减少肾脏胶原蛋白的积累,反映了肾脏羟脯氨酸,交联,反映了戊糖苷,脂质过氧化反应,糖氧化反应,反映了羧甲基赖氨酸,肾脏重量和蛋白尿的糖尿病小鼠。未处理动物的白蛋白尿与脂质过氧化密切相关。因此,我们在代表2型糖尿病的自发性糖尿病kk小鼠中的结果证实并扩展了最近在不同动物模型中精氨酸减少胶原蛋白的发现。其降低蛋白尿的机制可能与L-精氨酸阻断脂质过氧化产物有关。
In diabetic nephropathy a major current concept for pathogenesis is increased collagen accumulation in the glomerulus by increased collagen synthesis and decreased degradation. In the present study, we tested the hypothesis whether arginine is able to influence kidney lipid peroxidation, glycoxidation, collagen accumulation, glucose-mediated cross-linking, hydroxy radical attack, protein oxidation, nitric oxide formation and albuminuria in the diabetic kk mouse. Ten diabetic kk mice were given arginine 50 mg/kg body weight, 10 diabetic kk mice were not treated and used as negative controls and 10 kk mice were kept as healthy controls. Our results show that oral administration of low-dose arginine reduces kidney collagen accumulation as reflected by kidney hydroxyproline, cross-linking as reflected by pentosidine, lipid peroxidation, glycoxidation as reflected by carboxymethyl lysine, kidney weight and albuminuria in the diabetic Me mouse. Albuminuria in untreated animals was closely correlated with lipid peroxidation. Our results in the spontaneously diabetic kk mouse representing type 2 diabetes mellitus therefore confirm and extend recent findings of collagen reduction by arginine in a different animal model. The mechanism of reducing proteinuria can be assigned to the blocking of lipid peroxidation products by L-arginine.