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尼克罗米胺通过自噬途径减轻炎症细胞因子,从而改善肾缺血/再灌注损伤的预后。

Niclosamide attenuates inflammatory cytokines via the autophagy pathway leading to improved outcomes in renal ischemia/reperfusion injury.

机构信息

Department of Geriatrics, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China.

Department of Nephrology, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China.

出版信息

Mol Med Rep. 2017 Aug;16(2):1810-1816. doi: 10.3892/mmr.2017.6768. Epub 2017 Jun 14.

Abstract

Renal ischemia/reperfusion (I/R) injury is a debilitating condition that leads to loss renal function and damage to kidney tissue in the majority of patients with acute kidney disease. Previous studies have indicated that autophagy serves a protective function in renal I/R injury. In the present study, the effect of the anthelmintic niclosamide in the regulation of inflammatory responses in kidney I/R was investigated. A total of 40 Sprague-Dawley rats were randomly divided into the following 5 groups (n=8 in each group): Sham group; renal I/R injury; renal I/R injury plus 3‑methyladenine (3‑MA) treatment (15 mg/kg); renal I/R injury plus niclosamide (25 mg/kg); and renal I/R injury plus rapamycin (10 mg/kg). The expression levels of autophagy‑associated proteins in kidney samples obtained from rats with I/R injury were examined using reverse transcription‑quantitative polymerase chain reaction and western blotting techniques. In addition, histopathological alterations, the expression of cytokines and renal function were evaluated. Treatment with niclosamide was associated with induction of autophagy and an overall improvement in renal function. There was an increased expression of autophagosome‑associated proteins, suggesting a strong correlation between autophagy and improvement of renal function. The increased levels of anti‑inflammatory cytokines and decreased levels of pro‑inflammatory cytokines provided additional evidence that niclosamide may be effective for the treatment of renal I/R injury. Clinical studies are required to further validate the results of the present study.

摘要

肾缺血/再灌注(I/R)损伤是一种使大多数急性肾疾病患者的肾功能丧失和肾组织损伤的致残性疾病。先前的研究表明,自噬在肾 I/R 损伤中起保护作用。在本研究中,研究了驱虫药硝氯酚对肾 I/R 中炎症反应的调节作用。将 40 只 Sprague-Dawley 大鼠随机分为以下 5 组(每组 n=8):假手术组;肾 I/R 损伤组;肾 I/R 损伤加 3-甲基腺嘌呤(3-MA)治疗组(15mg/kg);肾 I/R 损伤加硝氯酚组(25mg/kg);肾 I/R 损伤加雷帕霉素组(10mg/kg)。采用逆转录-定量聚合酶链反应和蛋白质印迹技术检测 I/R 损伤大鼠肾组织中自噬相关蛋白的表达水平。此外,还评估了组织病理学改变、细胞因子的表达和肾功能。硝氯酚治疗与自噬的诱导和肾功能的整体改善有关。自噬体相关蛋白的表达增加,表明自噬与肾功能的改善之间存在很强的相关性。抗炎细胞因子水平的升高和促炎细胞因子水平的降低进一步表明,硝氯酚可能对肾 I/R 损伤的治疗有效。需要进行临床研究以进一步验证本研究的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bebc/5561795/4cd3765a5397/MMR-16-02-1810-g00.jpg

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