Advanced Glycation End-Product Levels in Subtotally Nephrectomized Rats: Beneficial Effects of Angiotensin II Receptor 1 Antagonist Losartan
Advanced Glycation End-Product Levels in Subtotally Nephrectomized Rats: Beneficial Effects of Angiotensin II Receptor 1 Antagonist Losartan
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肾次全切除大鼠的高级糖化终产物水平：血管紧张素 II 受体 1 拮抗剂氯沙坦的有益作用
DOI：
10.1159/000057478
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
A. Heidland
中科院分区：
文献类型：
--
作者：
K. Šebeková;R. Schinzel;G. Münch;Z. Krivosikova;R. Dzúrik;A. Heidland
在对肾小管上皮细胞进行的体外实验中，血管紧张素II受体1拮抗剂洛沙坦（L）可抑制晚期糖基化终产物（AGEs）诱导的转化生长因子β1的表达。为了测试这些发现的病理生理学的重要性，血清AGEs水平和血管紧张素系统之间的可能联系进行了研究，在模型中的血压正常的肾次全切除大鼠（4/6-NX）。如通过竞争性ELISA测量的，与假手术健康对照组（CTRL，n = 8，0.94±0.10 U/l，p<0.02）相比，给予安慰剂的4/6-NX大鼠（n = 7，1.09±0.09 U/l）的血清中AGEs浓度略微增加。用L治疗4/6-NX大鼠12周以上，改善了血清AGEs浓度的升高（1.00±0.12 U/l，n = 15 <0.005），几乎达到对照组观察到的水平。观察结果进一步证实了这一效应，即4/6-NX-安慰剂组大鼠（0.07±0.02 U/µmol肌酐）中受损的AGEs肾脏排泄可通过L（0.09±0.02 U/µmol肌酐，<0.009）显著恢复，与CTRL（0.10±0.03 U/µmol肌酐）相似。通过血清肌酐和尿素浓度的较小升高来评估，向4/6-NX大鼠施用L显著改善了肾功能。尽管肾功能有所改善，但两组间血清和尿液中转化生长因子β1浓度无差异。这些影响与血压无关。我们的数据提供了第一个证据，长期治疗血管紧张素II受体1拮抗剂可能会产生有益的影响，对AGEs水平的大鼠残肾模型，可能是由于改善肾功能。
The angiotensin II receptor 1 antagonist losartan (L) inhibited the advanced glycated end-products (AGEs) induced expression of transforming growth factor β1 in in vitro experiments performed on renal tubuloepithelial cells. To test the pathophysiological importance of these findings, the possible link between serum AGEs levels and angiotensin system was investigated in the model of normotensive subtotally nephrectomized rats(4/6-NX). Concentration of AGEs in serum of placebo administered 4/6-NX rats (n = 7, 1.09±0.09 U/l) increased slightly in comparison with sham-operated healthy controls (CTRL, n = 8, 0.94±0.10 U/l, p<0.02) as measured by competitive ELISA. Treatment of 4/6-NX rats with L over 12 weeks ameliorated the rise in serum AGEs concentration (1.00±0.12 U/l, n = 15 <0.005) almost to the level observed for CTRL. This effect was further corroborated by the observation, that the impaired renal excretion of AGEs in 4/6-NX-placebo rats (0.07±0.02 U/µmol creatinine) was significantly restored by L (0.09±0.02 U/µmol creatinine, <0.009) and resembled that of the CTRL (0.10±0.03 U/µmol creatinine). Administration of L to 4/6-NX rats significantly improved renal function as evaluated by a smaller rise in serum creatinine and urea concentration. In spite of the improvement in renal function, there were no differences in concentrations of transforming growth factor β1 in serum and in urine among the two groups. These effects were independent of blood pressure. Our data give first evidence, that long-term treatment with angiotensin II receptor 1 antagonist may exert salutary effects on AGEs levels in the rat remnant kidney model, probably due to improved renal function.
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DOI：
10.1016/s0021-9258(17)36966-1
发表时间：
1994-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Shi Du YanS;A. Schmidt;Mark Anderson;Jinghua Zhang;J. Brett;Y. Zou;D. Pinsky;David SternSn
通讯作者：
Shi Du YanS;A. Schmidt;Mark Anderson;Jinghua Zhang;J. Brett;Y. Zou;D. Pinsky;David SternSn
DOI：
10.1073/pnas.91.20.9441
发表时间：
1994-09-27
影响因子：
11.1
作者：
BUCALA, R;MAKITA, Z;VLASSARA, H
通讯作者：
VLASSARA, H
DOI：
10.1073/pnas.90.14.6434
发表时间：
1993-07-15
影响因子：
11.1
作者：
BUCALA, R;MAKITA, Z;VLASSARA, H
通讯作者：
VLASSARA, H
影响因子：
158.5
作者：
MAKITA, Z;RADOFF, S;VLASSARA, H
通讯作者：
VLASSARA, H
影响因子：
56.9
作者：
MONNIER, VM;CERAMI, A
通讯作者：
CERAMI, A