Restored nitric oxide bioavailability reduces the severity of acute-to-chronic transition in a mouse model of aristolochic acid nephropathy.
Restored nitric oxide bioavailability reduces the severity of acute-to-chronic transition in a mouse model of aristolochic acid nephropathy.
复制标题
恢复的一氧化氮生物利用度降低了亚里士醇胆道肾病的小鼠模型中急性到智种过渡的严重程度。
DOI：
10.1371/journal.pone.0183604
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Caron N
中科院分区：
文献类型：
--
作者：
Jadot I;Colombaro V;Martin B;Habsch I;Botton O;Nortier J;Declèves AE;Caron N
马兜铃酸 (AA) 肾病 (AAN) 是一种进行性肾小管间质性肾炎，其特征是早期急性肾损伤 (AKI) 导致慢性肾脏病 (CKD)。 AAN 中报告的一氧化氮 (NO) 生物利用度降低可能会导致肾功能损伤和疾病进展。我们之前证明，补充 L-精氨酸 (L-Arg) 对 AA 诱发的 AKI 具有保护作用。由于 AKI 的严重程度可能被认为是进展为 CKD 的有力预测因素，因此本研究旨在评估在 AAN 从急性期向慢性期过渡期间补充 L-Arg 的潜在益处。 C57BL/6J 雄性小鼠每天随机接受腹膜内注射。注射媒介物或AA 4天。为了确定 AA 引起的肾损伤是否与 NO 产生减少有关，从开始腹腔注射前 7 天开始，将 L-Arg 添加到饮用水中。注射，直至方案结束。给予载体或AA后5、10和20天对小鼠实施安乐死。 AA 治疗的小鼠表现出明显的肾损伤和 NO 生物利用度降低，同时再现了 AAN 的组织病理学特征，包括间质细胞浸润和肾小管间质纤维化。 L-Arg 治疗可恢复肾脏 NO 生物利用度，并减轻 AA 诱导的损伤、炎症和纤维化的严重程度。我们得出的结论是，肾脏 NO 生物利用度的降低有助于 AAN 的发生。此外，L-Arg 通过降低实验性 AAN 中急性向慢性转变的严重程度而显示出肾保护作用，并且可能代表未来潜在的治疗工具。
Aristolochic Acid (AA) nephropathy (AAN) is a progressive tubulointerstitial nephritis characterized by an early phase of acute kidney injury (AKI) leading to chronic kidney disease (CKD). The reduced nitric oxide (NO) bioavailability reported in AAN might contribute to renal function impairment and progression of the disease. We previously demonstrated that L-arginine (L-Arg) supplementation is protective in AA-induced AKI. Since the severity of AKI may be considered a strong predictor of progression to CKD, the present study aims to assess the potential benefit of L-Arg supplementation during the transition from the acute phase to the chronic phase of AAN. C57BL/6J male mice were randomly subjected to daily i.p. injections of vehicle or AA for 4 days. To determine whether renal AA-induced injuries were linked to reduced NO production, L-Arg was added to drinking water from 7 days before starting i.p. injections, until the end of the protocol. Mice were euthanized 5, 10 and 20 days after vehicle or AA administration. AA-treated mice displayed marked renal injury and reduced NO bioavailability, while histopathological features of AAN were reproduced, including interstitial cell infiltration and tubulointerstitial fibrosis. L-Arg treatment restored renal NO bioavailability and reduced the severity of AA-induced injury, inflammation and fibrosis. We concluded that reduced renal NO bioavailability contributes to the processes underlying AAN. Furthermore, L-Arg shows nephroprotective effects by decreasing the severity of acute-to-chronic transition in experimental AAN and might represent a potential therapeutic tool in the future.
登录
查看更多内容
影响因子：
5.6
作者：
Jadot I;Declèves AE;Nortier J;Caron N
通讯作者：
Caron N
DOI：
10.1016/j.bbrc.2012.06.049
发表时间：
2012-07-13
影响因子：
3.1
作者：
Li, Yi-Chieh;Tsai, Shin-Han;Lee, Jen-Ai
通讯作者：
Lee, Jen-Ai
DOI：
10.1186/1755-1536-5-s1-s15
发表时间：
2012
期刊：
Fibrogenesis & tissue repair
影响因子：
--
作者：
Guerrot D;Dussaule JC;Kavvadas P;Boffa JJ;Chadjichristos CE;Chatziantoniou C
通讯作者：
Chatziantoniou C
影响因子：
13.2
作者：
DEPIERREUX, M;VANDAMME, B;VANHERWEGHEM, JL
通讯作者：
VANHERWEGHEM, JL
影响因子：
2
作者：
Kurus, Meltem;Esrefoglu, Mukaddes;Ozturk, Feral
通讯作者：
Ozturk, Feral