Karimi Zeinab, Asadi Khatereh, Ghahramani Pooran, Gholami Ahmad
Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Sci Rep. 2024 Dec 30;14(1):32112. doi: 10.1038/s41598-024-83886-3.
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.
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。