白花蛇舌草多糖对异烟肼致肝损伤的影响及机制  

Effects and mechanism of polysaccharides from Hedyotis diffusa on isoniazid-induced liver injury

作　　者：庄秀萍 李莉[2] 陈超 王丽媛 曹广尚[3] 周朋[2] 王信[3] ZHUANG Xiuping;LI Li;CHEN Chao;WANG Liyuan;CAO Guangshang;ZHOU Peng;WANG Xin(School of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Dept.of Pediatrics,the Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250011,China;Dept.of Pharmacy,the Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250011,China)

机构地区：[1]山东中医药大学药学院,济南250355 [2]山东中医药大学附属医院儿科,济南250011 [3]山东中医药大学附属医院药学部,济南250011

出　　处：《中国药房》2024年第6期665-670,共6页China Pharmacy

基　　金：国家自然科学基金青年科学基金项目(No.8210-4506)。

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(4 mmol/L异烟肼)、HDP低浓度组(4 mmol/L异烟肼+50 mg/mL HDP)和HDP高浓度组(4 mmol/L异烟肼+100 mg/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。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 m

关 键 词：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 

分 类 号：R965[医药卫生—药理学] R285[医药卫生—药学]