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雷米迪维与地塞米松对雄性大鼠肾脏 Sirtuin-1 表达和肾功能的影响。

The Effects of Remdesivir and Dexamethasone on Renal Sirtuin-1 Expression and Renal Function in Male Rats.

机构信息

Department of Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Biotechnology Research Center, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz, Iran.

出版信息

Appl Biochem Biotechnol. 2024 Feb;196(2):632-642. doi: 10.1007/s12010-023-04529-3. Epub 2023 May 11.

DOI:10.1007/s12010-023-04529-3
PMID:37166648
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10172727/
Abstract

Remdesivir (REM) and dexamethasone (DEX) both have been used to treat coronavirus disease 2019 (COVID-19). The present study aimed to evaluate the effects of REM and DEX on kidney structure and function with particular focus on the probable renal sirtuin-1 (SIRT1) expression alteration in rats. Twenty-four male Wistar rats were divided into four groups, as follows: group A (control) received normal saline (5 mL/kg/day for 10 days); group B (REM) received REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days); group C (REM + DEX) received both REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days) and DEX (7 mg/kg/day, for 10 days); group D (DEX) received DEX (7 mg/kg/day for 10 days). Renal SIRT1 expression and kidney structure and function-related factors were evaluated by standard methods. The mean levels of urea in the REM + DEX group (60.83 ± 6.77, mg/dL) were significantly higher than in the control (48.33 ± 3.01, mg/dL; p = 0.002) and DEX (51.22 ± 4.99, mg/dL; p = 0.018) groups. The mean levels of creatinine in the REM (0.48 ± 0.08, mg/dL) and REM + DEX (0.50 ± 0.04, mg/dL) groups were higher than in the control group (48.33 ± 3.0 mg/dL) significantly (p = 0.022 and p = 0.010, respectively). The renal SIRT1 expression was significantly (p = 0.018) lower in the REM + DEX group (0.36 ± 0.35) than in the control group (1.34 ± 0.48). Tubulointerstitial damage (TID) scores in REM + DEX-treated rats (2.60 ± 0.24) were significantly higher than in the control (0.17 ± 0.17, p = 0.001) and DEX (0.50 ± 0.29, p = 0.005) groups. The administration of DEX and REM might lead to kidney injury associated with SIRT1 downregulation.

摘要

瑞德西韦(REM)和地塞米松(DEX)都被用于治疗 2019 年冠状病毒病(COVID-19)。本研究旨在评估 REM 和 DEX 对肾脏结构和功能的影响,特别关注大鼠肾脏中 SIRT1 表达可能发生的改变。将 24 只雄性 Wistar 大鼠分为四组:A 组(对照组)给予生理盐水(5 mL/kg/天,共 10 天);B 组(REM 组)给予 REM(第 1 天 17 mg/kg,第 2-10 天 8.5 mg/kg);C 组(REM+DEX 组)给予 REM(第 1 天 17 mg/kg,第 2-10 天 8.5 mg/kg)和 DEX(7 mg/kg/天,共 10 天);D 组(DEX 组)给予 DEX(7 mg/kg/天,共 10 天)。采用标准方法评估肾脏 SIRT1 表达和与肾脏结构和功能相关的因素。与对照组(48.33±3.01,mg/dL;p=0.002)和 DEX 组(51.22±4.99,mg/dL;p=0.018)相比,REM+DEX 组(60.83±6.77,mg/dL)的尿素平均值明显更高。与对照组(48.33±3.01,mg/dL)相比,REM(0.48±0.08,mg/dL)和 REM+DEX(0.50±0.04,mg/dL)组的肌酐平均值明显更高(p=0.022 和 p=0.010)。与对照组(1.34±0.48)相比,REM+DEX 组(0.36±0.35)的肾脏 SIRT1 表达明显降低(p=0.018)。与对照组(0.17±0.17,p=0.001)和 DEX 组(0.50±0.29,p=0.005)相比,接受 REM+DEX 治疗的大鼠的肾小管间质损伤(TID)评分(2.60±0.24)明显更高。给予 DEX 和 REM 可能导致与 SIRT1 下调相关的肾脏损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838f/10172727/7a892e83321d/12010_2023_4529_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838f/10172727/e503bee5ecc5/12010_2023_4529_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838f/10172727/2e27647ff17f/12010_2023_4529_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838f/10172727/7a892e83321d/12010_2023_4529_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838f/10172727/e503bee5ecc5/12010_2023_4529_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838f/10172727/2e27647ff17f/12010_2023_4529_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838f/10172727/7a892e83321d/12010_2023_4529_Fig3_HTML.jpg

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Remdesivir Alleviates Acute Kidney Injury by Inhibiting the Activation of NLRP3 Inflammasome.瑞德西韦通过抑制NLRP3炎性小体的激活减轻急性肾损伤。
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