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有读书笔记Disparate effects on renal and oxidative parameters following RAGE deletion, AGE accumulation inhibition or dietary AGE control in diabetic nephropathy

热2 shenww 添加于 2009-12-19 11:47 | 2601 次阅读 | 1 个评论

  •  作 者

    Tan AL, Sourris KC, Harcourt BE, Thallas-Bonke V, Penfold S, Andrikopoulos S P, Thomas MC, O'Brien RC, Bierhaus A, Cooper ME, Forbes JM, Coughlan MT

  •  摘 要

    Advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE) generate ROS and therefore this study evaluated the effects of RAGE-deletion, decreasing AGE accumulation or lowering dietary AGE content on oxidative parameters in diabetic nephropathy (DN). Control and diabetic male wild-type and RAGE-deficient (RAGE(-/-)) mice were fed high or low AGE diets, with two groups given the inhibitor of AGE accumulation, alagebrium chloride and followed for 24 weeks. Diabetic RAGE(-/-) mice were protected against albuminuria, hyperfiltration, glomerulosclerosis, decreased renal mitochondrial ATP production and excess generation of both mitochondrial and cytosolic superoxide. While glomerulosclerosis, tubulointerstitial expansion and hyperfiltration were improved in diabetic mice treated with alagebrium, there was no effect on urinary albumin excretion. Both diabetic RAGE(-/-) and alagebrium treated mice had an attenuation of renal RAGE expression and decreased renal and urinary AGE (CML) levels. Low AGE diets did not confer renoprotection, lower the AGE burden or renal RAGE expression nor improve cytosolic or mitochondrial superoxide generation. Renal uncoupling protein-2 gene expression and mitochondrial membrane potential were attenuated by all therapeutic interventions in diabetic mice. In the present study, diverse approaches to block the AGE-RAGE axis have disparate effects on DN, which has potential clinical implications for the way this axis should be targeted in man. Key words: diabetic nephropathy, oxidative stress, RAGE, advanced glycation.

  •  详细资料

    • 文献种类:期刊
    • 期刊名称: American Journal of Physiology. Renal Physiology
    • 期刊缩写: Am J Physiol Renal Physiol
    • 期卷页: 2009年
    • 地址: Baker IDI Heart and Diabetes Institute
    • ISBN: 1522-1466
    • 备注:PMID:20015941

  •  标 签

    diabetes  ROS  AGEs  RAGE 

  • 相关链接 DOI URL 

  •  shenww 的文献笔记  订阅

    糖尿病+RAGE(-/-)+AGEs饮食：白蛋白尿、高滤过、肾小球硬化、肾线粒体ATP合成、线粒体和细胞质超氧化物的形成均得到改善。

    糖尿病+RAGE（+/+）+AGEs饮食+algebrium抗AGEs治疗：肾小球硬化、小管间质增宽、高滤过改善，但白蛋白尿持续存在。

    两者均有RAGE和肾/尿CML的表达减少

    低AGEs饮食未见有保护作用。

    以上三种均能减少UCP2的表达。

    points：体内合成AGEs在糖尿病中起到更大作用；RAGE是否有另于AGEs引发的信号传递？algebrium是否能彻底抑制AGEs的聚集？

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