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负载三硝酸甘油的壳聚糖纳米颗粒通过调节氧化应激减轻肾脏缺血再灌注损伤。

Trinitroglycerine-loaded chitosan nanoparticles attenuate renal ischemia-reperfusion injury by modulating oxidative stress.

作者信息

Karimi Zeinab, Asadi Khatereh, Ghahramani Pooran, Gholami Ahmad

机构信息

Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Sci Rep. 2024 Dec 30;14(1):32112. doi: 10.1038/s41598-024-83886-3.

Abstract

Renal ischemia-reperfusion (I/R) injury is a common clinical factor for acute kidney injury (AKI). A current study investigated the renoprotective effects of the trinitroglycerine (TNG) combination with chitosan nanoparticles (CNPs) on renal I/R-induced AKI. Rats were randomly assigned to five groups (n = 8/group): Sham, I/R, TNG (50 mg/kg) + I/R, CNPs (60 mg/kg) + I/R, and TNG-CNPs + I/R. Bilateral renal pedicles were occluded for 60 min to induce ischemia. TNG, CNPs, or TNG-CNPs were administered intraperitoneally 30 min before renal ischemia. After 24 h of reperfusion, blood samples were collected, and both kidneys were removed. The left kidney was used for oxidative stress analysis. The right kidney was preserved in 10% formalin for histopathological examination via H&E staining. After renal ischemia-reperfusion injury, there was an observed increase in plasma creatinine (Cr) and blood urea nitrogen (BUN), accompanied by a decrease in glomerular filtration rate (GFR) in rats. Total oxidative stress (TOS) levels were also significantly higher in the I/R group, whereas total antioxidative capacity (TAC) was reduced. Histopathological examination revealed damage in the kidneys of rats in the I/R group. Pretreatment with the TNG-CNP formulation before I/R increased plasma and tissue TAC levels in rats. It also corrected the renal histopathological changes and functional disorders induced by I/R injury, as evidenced by reduced Cr and BUN, increased GFR, and attenuated oxidative stress. The results suggest that the TNG-CNP combination provides renoprotective effects against I/R-induced AKI by improving antioxidant status and minimizing renal injury.

摘要

肾缺血再灌注(I/R)损伤是急性肾损伤(AKI)常见的临床因素。当前一项研究调查了三硝酸甘油(TNG)与壳聚糖纳米粒(CNP)联合使用对肾I/R诱导的AKI的肾脏保护作用。将大鼠随机分为五组(每组n = 8):假手术组、I/R组、TNG(50 mg/kg)+ I/R组、CNP(60 mg/kg)+ I/R组以及TNG-CNP + I/R组。双侧肾蒂阻断60分钟以诱导缺血。在肾缺血前30分钟腹腔注射TNG、CNP或TNG-CNP。再灌注24小时后,采集血样并摘除双侧肾脏。左肾用于氧化应激分析。右肾保存于10%福尔马林中,通过苏木精-伊红(H&E)染色进行组织病理学检查。肾缺血再灌注损伤后,观察到大鼠血浆肌酐(Cr)和血尿素氮(BUN)升高,同时肾小球滤过率(GFR)降低。I/R组的总氧化应激(TOS)水平也显著更高,而总抗氧化能力(TAC)降低。组织病理学检查显示I/R组大鼠肾脏有损伤。I/R前用TNG-CNP制剂预处理可提高大鼠血浆和组织中的TAC水平。它还纠正了I/R损伤诱导的肾脏组织病理学变化和功能紊乱,表现为Cr和BUN降低、GFR升高以及氧化应激减轻。结果表明,TNG-CNP联合使用通过改善抗氧化状态和最小化肾损伤,对I/R诱导的AKI具有肾脏保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f62/11685805/13593c4796ee/41598_2024_83886_Fig1_HTML.jpg

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