N-acetylcysteine ameliorates hematuria-associated tubulointerstitial injury in 5/6 nephrectomy mice.
N-acetylcysteine ameliorates hematuria-associated tubulointerstitial injury in 5/6 nephrectomy mice.
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DOI：
10.14814/phy2.15767
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发表时间：
2023-07
影响因子：
2.5
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中科院分区：
文献类型：
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慢性肾病（CKD）的特点是肾脏间质纤维化和肾小管萎缩（IFTA）增加。慢性血尿是多种人类肾脏疾病的标志，经常出现在接受抗凝治疗的患者中。我们之前已经证明，与华法林相关的慢性血尿会增加 5/6 肾切除 (5/6NE) 大鼠的 IFTA，并且这种治疗会增加肾脏中的活性氧 (ROS)。本研究的目的是评估抗氧化剂 N-乙酰半胱氨酸 (NAC) 对 5/6NE 小鼠 IFTA 进展的影响。将5/6NE C57BL/6和5/6NE 129S1/SvImJ小鼠单独用华法林或用华法林和NAC治疗23周。测量血清肌酐（SCr）、血尿、血压（BP）和肾脏中的ROS；评估肾脏形态。滴定华法林剂量以使凝血酶原时间 (PT) 增加至人类治疗剂量的水平。华法林治疗导致两种小鼠品系的肾脏 SCr、收缩压、血尿、TGF-β 和 ROS 表达增加。接受华法林治疗的 5/6NE 小鼠血清中肿瘤坏死因子 α (TNF-ɑ) 水平升高。与对照5/6NE小鼠相比，IFTA增加，并且IFTA的增加在129S1/SvImJ中比在C57BL/6小鼠中更显着。 NAC 改善了华法林相关的 SCr 和血压升高，但没有改善血尿。与单独使用华法林治疗的小鼠相比，使用 NAC 和华法林治疗的小鼠肾脏中的 IFTA、TGF-β 和 ROS 以及血清中的 TNF-α 水平降低。 NAC 通过减少肾脏的氧化应激来减轻慢性血尿小鼠 SCr 和 IFTA 的增加。该数据为 CKD 患者的治疗开辟了新的可能性。
Chronic kidney disease (CKD) is characterized by increased interstitial fibrosis and tubular atrophy (IFTA) in the kidney. Chronic hematuria is a hallmark of several human kidney diseases and often is seen in patients on anticoagulation therapy. We had previously demonstrated that chronic hematuria associated with warfarin increases IFTA in 5/6 nephrectomy (5/6NE) rats, and such treatment increases reactive oxygen species (ROS) in the kidney. The goal of this study was to evaluate the effects of the antioxidant N‐acetylcysteine (NAC) on the progression of IFTA in 5/6NE mice. 5/6NE C57BL/6 and 5/6NE 129S1/SvImJ mice were treated with warfarin alone or with warfarin and NAC for 23 weeks. Serum creatinine (SCr), hematuria, blood pressure (BP), and ROSs in the kidney were measured; kidney morphology was evaluated. Warfarin doses were titrated to achieve prothrombin time (PT) increase to the levels seen with therapeutic human doses. Warfarin treatment resulted in an increased SCr, systolic BP, hematuria, expression of TGF‐ß and ROS in the kidney in both mouse strains. Tumor necrosis factor alpha (TNF‐ɑ) levels in the serum were increased in 5/6NE mice treated with warfarin. IFTA was increased as compared with control 5/6NE mice, and this increase in IFTA was more prominent in 129S1/SvImJ than in C57BL/6 mice. NAC ameliorated the warfarin‐associated increase in SCr and BP but not hematuria. IFTA, TGF‐ß, and ROS in the kidney as well as TNF‐ɑ levels in the serum were reduced in mice treated with NAC and warfarin as compared to mice treated with warfarin alone. NAC mitigates the increase in SCr and IFTA in mice with chronic hematuria by reducing oxidative stress in the kidney. This data open novel possibilities for treatments in CKD patients.
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影响因子：
4.2
作者：
Ozcan, A.;Ware, K.;Brodsky, S. V.
通讯作者：
Brodsky, S. V.
影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
5.1
作者：
Dong, Wenxuan;Zhang, Kanglei;Liu, Zongping
通讯作者：
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