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芫花素通过调节氧化应激、炎症和核因子 kappa B/ toll 样受体 4 通路对小鼠肝缺血/再灌注损伤的保护作用。

Protective effect of liriodendrin against liver ischaemia/reperfusion injury in mice via modulating oxidative stress, inflammation and nuclear factor kappa B/toll-like receptor 4 pathway.

机构信息

Department of General Surgery, Panjin Central Hospital, Panjin, Liaoning Province, China.

Department of Intensive Care Unit, The People's Hospital of Shimen County, Changde, Hunan Province, China.

出版信息

Folia Morphol (Warsz). 2023;82(3):668-676. doi: 10.5603/FM.a2022.0049. Epub 2022 May 24.

Abstract

BACKGROUND

The aim of the present study was to investigate the protective effect and mechanism of liriodendrin (LDN) is a lignan diglucoside in hepatic ischaemia/ /reperfusion (I/R) injury.

MATERIALS AND METHODS

The liver I/R was established in male C57BL/6 mice. The effect of LDN is initially investigated on hepatic I/R injury via estimating histopathology of liver. The level of metabolic enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) was studied along with apoptosis of mouse hepatocytes via TUNEL and flow cytometry analysis. The effect of LDN was investigated on oxidative stress biomarkers (glutathione [GSH] content, malondialdehyde [MDA] and superoxide dismutase [SOD] activities) and pro-inflammatory cytokines (tumour necrosis factor alpha [TNF-α], interleukin [IL]-1β and IL-6). Western blot study was also conducted to elucidate the effect of LDN on toll-like receptor 4/nuclear factor kappa B (TLR4/NF-kB).

RESULTS

Liriodendrin alleviates liver I/R injury, as manifested by decreased plasma ALT, AST and ALP with improvement in liver necrotic area. LDN also reduces apoptosis of mouse hepatocytes with reduction of oxidative stress and generation of pro-inflammatory cytokines. It significantly reduces the expression of TLR4 and NF-kB.

CONCLUSIONS

The study demonstrated that LDN reduces liver injury and prevented apoptosis of hepatocytes following I/R injury. In addition, LDN also reduces oxidative stress, inflammation, and TLR4/NF-kB in I/R injured mice.

摘要

背景

本研究旨在探讨松脂素(LDN)作为一种木脂素双葡萄糖苷对肝缺血/再灌注(I/R)损伤的保护作用及其机制。

材料与方法

采用雄性 C57BL/6 小鼠建立肝 I/R 模型。通过评估肝组织病理学,初步研究 LDN 对肝 I/R 损伤的影响。通过 TUNEL 和流式细胞术分析研究代谢酶丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和碱性磷酸酶(ALP)以及小鼠肝细胞凋亡的水平。通过测定氧化应激生物标志物(谷胱甘肽[GSH]含量、丙二醛[MDA]和超氧化物歧化酶[SOD]活性)和促炎细胞因子(肿瘤坏死因子-α[TNF-α]、白细胞介素[IL]-1β和 IL-6)来研究 LDN 的作用。还进行了 Western blot 研究以阐明 LDN 对 Toll 样受体 4/核因子 kappa B(TLR4/NF-kB)的影响。

结果

松脂素减轻了肝 I/R 损伤,表现为血浆 ALT、AST 和 ALP 降低,肝坏死面积改善。LDN 还减少了小鼠肝细胞的凋亡,降低了氧化应激和促炎细胞因子的产生。它显著降低了 TLR4 和 NF-kB 的表达。

结论

本研究表明,LDN 可减少 I/R 损伤后肝损伤和肝细胞凋亡。此外,LDN 还可减少 I/R 损伤小鼠的氧化应激、炎症和 TLR4/NF-kB。

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