白花蛇舌草多糖对异烟肼致肝损伤的影响及机制
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篇名: 白花蛇舌草多糖对异烟肼致肝损伤的影响及机制
TITLE: Effects and mechanism of polysaccharides from Hedyotis diffusa on isoniazid-induced liver injury
摘要: 目的 探讨白花蛇舌草多糖(HDP)对异烟肼致肝损伤的影响及机制。方法以正常发育的具有肝脏特异性荧光的转基因斑马鱼为对象,分为正常组、模型组(4mmol/L异烟肼)、HDP低浓度组(4mmol/L异烟肼+50mg/mLHDP)和HDP高浓度组(4mmol/L异烟肼+100mg/mLHDP),分组处理后观察斑马鱼肝脏荧光面积、荧光强度以及肝组织病理变化。以人肝L02细胞为对象,分为正常组、模型组(4mmol/L异烟肼)、HDP低浓度组(4mmol/L异烟肼+2mg/mLHDP)和HDP高浓度组(4mmol/L异烟肼+4mg/mLHDP),分组处理后检测细胞存活情况,细胞上清液中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平及细胞裂解液中谷胱甘肽(GSH)含量,沉默信息调节因子1(Sirt1)、核转录因子红系2相关因子2(Nrf2)、血红素加氧酶1(HO-1)、醌氧化还原酶1(NQO1)蛋白的表达水平。结果与模型组比较,HDP低、高浓度组斑马鱼肝脏荧光面积和荧光强度(HDP低浓度组除外)均显著增加(P<0.05或P<0.01),肝损伤坏死特征均有不同程度改善。与模型组比较,HDP低、高浓度组L02细胞存活率,GSH含量(HDP低浓度组除外),Sirt1(HDP低浓度组除外)、Nrf2、NQO1、HO-1(HDP低浓度组除外)蛋白表达水平均显著升高(P<0.05或P<0.01);ALT、AST(HDP低浓度组除外)水平均显著降低(P<0.05);存活细胞数量均明显增加,损伤或死亡细胞数量均明显减少。结论HDP对异烟肼诱导的肝损伤具有一定的改善作用,其机制可能与激活Sirt1/Nrf2信号通路、改善线粒体功能、提高抗氧化能力相关。
ABSTRACT: OBJECTIVE To investigate the effects and mechanism of polysaccharides from Hedyotis diffusa (HDP) on isoniazid (INH)-induced liver injury. METHODS Healthy transgenic zebrafish with liver-specific fluorescence were divided into normal group, model group (4 mmol/L INH), HDP low-concentration group (4 mmol/L INH+50 mg/mL HDP) and HDP high- concentration group (4 mmol/L INH+100 mg/mL HDP). After grouping treating, the liver fluorescence area, fluorescence intensity and pathological changes of liver tissue were observed. Human liver L02 cells were divided into normal group, model group (4 mmol/L INH), HDP low-concentration group (4 mmol/L INH+2 mg/mL HDP), and HDP high-concentration group (4 mmol/L INH + 4 mg/mL HDP). After grouping treating, the cell viability was detected, and the levels of alanine transaminase (ALT), aspartate transaminase (AST), and the content of glutathione (GSH) as well as the expression levels of silent information regulator 1 (Sirt1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) proteins were detected. RESULTS Compared with the model group, the HDP low- and high-concentration groups showed varying degrees of increase in the fluorescence area and fluorescence intensity (except for HDP low-concentration group) of zebrafish liver (P<0.05 or P<0.01), and the characteristics of liver injury and necrosis had been improved to varying degrees. Compared with model group, the survival rate of L02 cells, the content of GSH (except for HDP low-concentration group), the protein expression levels of Sirt1 (except for HDP low-concentration group), Nrf2, NQO1, HO-1 (except for HDP low-concentration group) were significantly increased in HDP low- and high-concentration groups (P<0.05 or P<0.01), and the levels of ALT and AST (except for HDP low-concentration group) were significantly decreased (P<0.05); the number of survival cells significantly increased, while the number of damaged or dead cells significantly decreased. CONCLUSIONS HDP has a potential protective effect against INH-induced liver injury, the mechanism of which may be associated with activating Sirt1/Nrf2 signaling pathway, improving mitochondrial function and enhancing antioxidant capacity.
期刊: 2024年第35卷第06期
作者: 庄秀萍;李莉;陈超;王丽媛;曹广尚;周朋;王信
AUTHORS: ZHUANG Xiuping,LI Li,CHEN Chao,WANG Liyuan,CAO Guangshang,ZHOU Peng,WANG Xin
关键字: 白花蛇舌草多糖;异烟肼;肝损伤;斑马鱼;人肝L02细胞;Sirt1/Nrf2信号通路
KEYWORDS: polysaccharides from Hedyotis diffusa;
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