Agmatine inhibits cell proliferation and improves renal function in anti-thy-1 glomerulonephritis.
Agmatine inhibits cell proliferation and improves renal function in anti-thy-1 glomerulonephritis.
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发表时间：
2000-12
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通讯作者：
S. Ishizuka;R. Cunard;S. Poucell-Hatton;L. Wead;M. Lortie;S. Thomson;F. Gabbai;J. Satriano;R. Blantz
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作者：
S. Ishizuka;R. Cunard;S. Poucell-Hatton;L. Wead;M. Lortie;S. Thomson;F. Gabbai;J. Satriano;R. Blantz
精氨酸替代代谢途径表达的变化与实验性肾小球肾炎的发病机制有关。Agmatine是一种脱羧精氨酸，在体外已被证明可以抑制诱导型一氧化氮合酶和多胺生物合成的限速酶鸟氨酸脱羧酶（ODC）。本研究旨在确定在实验性系膜增殖性肾小球肾炎（ty -1肾炎）中，agmatine给药是否可以通过降低一氧化氮来减轻组织损伤，并通过降低ODC活性来减少细胞增殖。在Thy-1肾炎大鼠中，Agmatine治疗（50 mg/kg / d腹腔注射）在第1天阻止了GFR的降低。在第1天和第4天，Agmatine治疗使Thy-1肾炎大鼠一氧化氮的产生分别减少23%和41%。Agmatine治疗在第1、4和7天也降低了ODC活性和肾小球h -胸腺嘧啶掺入。组织学评估显示，在Thy-1抗体前或抗体后24小时给予agmatine治疗，系膜细胞增殖和细胞外基质积累下降，并且在第4天和第7天表达增殖细胞核抗原的细胞数量减少证实了这一点。这些研究首次提供了体内证据，证明agmatine给药可以减少Thy-1肾炎的细胞增殖，并减轻与该模型相关的肾功能的初始降低。
Changes in the expression of alternate arginine metabolic pathways have been implicated in the pathogenesis of experimental glomerulonephritis. Agmatine, decarboxylated arginine, has been shown in vitro to suppress both inducible nitric oxide synthase and the rate-limiting enzyme of polyamine biosynthesis, ornithine decarboxylase (ODC). This study was undertaken to determine whether agmatine administration could reduce tissue injury by decreasing nitric oxide, and reduce cell proliferation, by diminishing ODC activity, in experimental mesangial proliferative glomerulonephritis (Thy-1 nephritis). Agmatine treatment (50 mg/kg per d intraperitoneally) in Thy-1 nephritis rats prevented a reduction in GFR at day 1. Agmatine treatment decreased nitric oxide production in Thy-1 nephritis rats by 23% and 41% at days 1 and 4, respectively. Agmatine treatment also reduced ODC activity and glomerular (3)H-thymidine incorporation on days 1, 4, and 7. Histologic evaluation revealed a decline in mesangial cell proliferation and extracellular matrix accumulation associated with agmatine treatment administered before or 24 h after Thy-1 antibody, and this was confirmed by a reduction in the number of cells expressing proliferating cell nuclear antigen on days 4 and 7. These studies provide the first in vivo evidence that agmatine administration can reduce cellular proliferation in Thy-1 nephritis and attenuate the initial reduction in renal function associated with this model.