NO mediates antifibrotic actions of L-arginine supplementation following induction of anti-thy1 glomerulonephritis.
NO mediates antifibrotic actions of L-arginine supplementation following induction of anti-thy1 glomerulonephritis.
复制标题
NO 介导抗 thy1 肾小球肾炎诱导后补充 L-精氨酸的抗纤维化作用。
作者：
H. Peters;U. Daig;S. Martini;Matthias Rückert;F. Schäper;L. Liefeldt;S. Krämer;H. Neumayer
未标记
NO介导L-精氨酸补充抗纤维化作用后诱导抗-thy 1肾小球肾炎。
背景
L-精氨酸在肾基质扩张中起着复杂的作用，涉及内源性代谢为一氧化氮（NO）、多胺、L-脯氨酸和胍丁胺。补充膳食L-精氨酸摄入量已被证明限制转化生长因子（TGF）-β 1的过度生产和基质积累诱导抗甲状腺素1肾小球肾炎（GN）大鼠。目前的研究测试的假设，这种有益的影响，在体内TGF-β过表达介导的NO的产生。
方法
在诱导抗thy 1 GN后1天，将喂食正常蛋白质饮食的雄性Wistar大鼠分为以下组：（1）正常对照组;（2）GN组;（3）GN-Arg组（4）GN-Arg-NAME [在饮用水中添加500 mg L-精氨酸/天和75 mg/L NO合酶抑制剂硝基-L-精氨酸-甲酯（L-NAME）];和（5）GN-Molsi（10 mg/天的NO供体吗西多明）。在方案1中，治疗持续至疾病诱导后第7天，在方案2中，治疗持续至疾病诱导后第12天。分析包括收缩压、肾小球组织学基质评分、关键纤维原TGF-β 1、基质蛋白纤连蛋白和蛋白酶抑制剂纤溶酶原激活物抑制剂1（派-1）的肾小球mRNA和蛋白表达。
结果
未处理的抗-thy 1动物的血压正常，未受到任何处理的显著影响。与未治疗的肾炎大鼠相比，L-精氨酸和吗多明的管理减少肾小球TGF-β 1的过度表达显着，并在两个协议的相似程度，而L-精氨酸的有益效果被取消伴随NO合成抑制。肾小球基质积聚、纤连蛋白和派-1 mRNA和蛋白表达紧随TGF-β 1的表达。
结论
目前的研究表明，L-精氨酸的抗纤维化作用在血压正常的抗甲状腺1 GN主要是介导的内源性生产的NO。数据表明，NO限制在体内TGF-β过表达的压力不依赖的方式和NO捐助者可能是有益的治疗人类纤维化肾病。
UNLABELLED
NO mediates antifibrotic actions of L-arginine supplementation following induction of anti-thy1 glomerulonephritis.
BACKGROUND
L-Arginine plays a complex role in renal matrix expansion, involving endogenous metabolism into nitric oxide (NO), polyamines, L-proline and agmatine. Supplementing dietary L-arginine intake has been shown to limit transforming growth factor (TGF)-beta 1 overproduction and matrix accumulation in rats with induced anti-thy1 glomerulonephritis (GN). The present study tests the hypothesis that this beneficial effect on in vivo TGF-beta overexpression is mediated via the generation of NO.
METHODS
One day after induction of anti-thy1 GN, male Wistar rats fed a normal protein diet were assigned to the following groups: (1) normal controls; (2) GN; (3) GN-Arg (plus 500 mg L-arginine/day); (4) GN-Arg-NAME [plus 500 mg L-arginine/day and 75 mg/L of the NO synthase inhibitor nitro-L-arginine-methyl ester (L-NAME) in the drinking water]; and (5) GN-Molsi (10 mg/day of the NO donor molsidomine). In protocol 1, treatment lasted until day 7, and in protocol 2, until day 12 after disease induction, respectively. Analysis included systolic blood pressure, a glomerular histologic matrix score, and the glomerular mRNA and protein expression of the key fibrogen TGF-beta1, the matrix protein fibronectin, and the protease inhibitor plasminogen activator inhibitor type 1 (PAI-1).
RESULTS
Blood pressure was normal in untreated anti-thy1 animals and not significantly affected by any of the treatments. Compared to untreated nephritic rats, administration of both L-arginine and molsidomine reduced glomerular TGF-beta 1 overexpression significantly and to a similar degree in both protocols, while the beneficial effect of L-arginine was abolished by concomitant NO synthesis inhibition. Glomerular matrix accumulation, fibronectin and PAI-1 mRNA and protein expression closely followed the expression of TGF-beta 1.
CONCLUSION
The present study shows that L-arginine's antifibrotic action in normotensive anti-thy1 GN is mainly mediated by endogenous production of NO. The data suggest that NO limits in vivo TGF-beta overexpression in a pressure-independent manner and that NO donors may be of benefit in the treatment of human fibrotic renal disease.
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DOI：
10.1073/pnas.120055097
发表时间：
2000-07-05
影响因子：
11.1
作者：
Ziyadeh, FN;Hoffman, BB;Sharma, K
通讯作者：
Sharma, K
影响因子：
2.9
作者：
GREEN, LC;WAGNER, DA;TANNENBAUM, SR
通讯作者：
TANNENBAUM, SR
DOI：
--
发表时间：
2000-12
期刊：
Journal of the American Society of Nephrology : JASN
影响因子：
--
作者：
S. Ishizuka;R. Cunard;S. Poucell-Hatton;L. Wead;M. Lortie;S. Thomson;F. Gabbai;J. Satriano;R. Blantz
通讯作者：
S. Ishizuka;R. Cunard;S. Poucell-Hatton;L. Wead;M. Lortie;S. Thomson;F. Gabbai;J. Satriano;R. Blantz
一氧化氮介导实验性肾小球肾炎中肾系膜的免疫损伤。
DOI：
--
发表时间：
1995
期刊：
Laboratory investigation; a journal of technical methods and pathology.
影响因子：
--
作者：
Narita,I;Border,WA;Ketteler,M;Noble,NA
通讯作者：
Noble,NA
影响因子：
15.9
作者：
CHEN, PY;SANDERS, PW
通讯作者：
SANDERS, PW