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吡哆胺通过调节KK-Ay/Ta小鼠中CD36的表达对糖尿病并发症产生多效性作用。

Pleiotropic effect of pyridoxamine on diabetic complications via CD36 expression in KK-Ay/Ta mice.

作者信息

Murakoshi Maki, Tanimoto Mitsuo, Gohda Tomohito, Hagiwara Shinji, Ohara Ikko, Toyoda Hitoe, Ishikawa Yuji, Horikoshi Satoshi, Tomino Yasuhiko

机构信息

Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.

出版信息

Diabetes Res Clin Pract. 2009 Feb;83(2):183-9. doi: 10.1016/j.diabres.2008.11.008. Epub 2009 Jan 13.

Abstract

AIM

Pyridoxamine inhibits the development of diabetic complications. CD36 is a receptor/transporter which binds fatty acids of lipoproteins. The objective of the present study was to examine the pleiotropic effects of pyridoxamine, especially CD36 expression in KK-A(y)/Ta mice with type 2 diabetic nephropathy.

METHODS

KK-A(y)/Ta mice were divided into 2 groups as follows: pyridoxamine treatment group and a tap water group as controls. The urinary ACR, fasting serum insulin, TG and lipoprotein subclasses were measured as biochemical parameters. The renal expressions of malondialdehyde (MDA) were evaluated by immunohistochemistry. CD36 mRNA expressions in kidney and adipose tissue were also evaluated using real-time PCR.

RESULTS

Pyridoxamine decreased levels of urinary ACR, serum TG, especially VLDL and fasting serum insulin. MDA accumulation in the pyridoxamine treated group was significantly lower than those in the non-treatment group. The CD36 accumulation and mRNA expressions in kidney and adipose tissue in the treatment group were significantly higher than those in the non-treatment group.

CONCLUSIONS

It appears that pyridoxamine ameliorated lipid peroxidation and insulin resistance in KK-A(y)/Ta mice. This pleiotropic effect of pyridoxamine was related to CD36 expression in the kidney and adipose tissue.

摘要

目的

吡哆胺可抑制糖尿病并发症的发展。CD36是一种能结合脂蛋白脂肪酸的受体/转运蛋白。本研究的目的是探讨吡哆胺的多效性作用,尤其是其对2型糖尿病肾病KK-A(y)/Ta小鼠CD36表达的影响。

方法

将KK-A(y)/Ta小鼠分为两组:吡哆胺治疗组和自来水对照组。检测尿ACR、空腹血清胰岛素、甘油三酯(TG)和脂蛋白亚类作为生化指标。采用免疫组化法评估肾组织中丙二醛(MDA)的表达。同时利用实时定量PCR评估肾组织和脂肪组织中CD36 mRNA的表达。

结果

吡哆胺可降低尿ACR、血清TG水平,尤其是极低密度脂蛋白(VLDL)水平以及空腹血清胰岛素水平。吡哆胺治疗组的MDA蓄积量显著低于未治疗组。治疗组肾组织和脂肪组织中CD36的蓄积量及mRNA表达水平均显著高于未治疗组。

结论

吡哆胺似乎改善了KK-A(y)/Ta小鼠的脂质过氧化和胰岛素抵抗。吡哆胺的这种多效性作用与肾组织和脂肪组织中CD36的表达有关。

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