摘要
目的:通过NF-κB/TLR4/Nrf2信号通路探讨钩藤天麻药对治疗雷公藤多苷片导致的药物性肝损伤作用及分子机制。方法:随机将雄性SPF级BALB/c小鼠分为6组,3组为钩藤天麻药对组(剂量分别为8.125 g·kg^(-1) d^(-1)、16.250 g·kg^(-1)·d^(-1)、32.500 g·kg^(-1)·d^(-1)),阳性对照组(水飞蓟宾0.480 g·kg^(-1)),空白对照组和模型组(雷公藤多苷片0.300 g·kg^(-1))。末次给药24h后摘眼球取血,并进行ALT和AST活性测定;处死、取肝脏并进行谷胱甘肽、超氧化物歧化酶、丙二醛含量测定,Elisa检测TNF-α、过氧化脂质含量;肝组织进行HE染色及Western blot检测NF-κB,TLR4和Nrf2蛋白表达。结果:与正常组比较,模型组中的ALT、AST、SOD、MDA、GSH-Px、LPO及TNF-α水平均显著升高(P<0.01),肝组织结构重度异常,出现肝细胞脂肪变性,胞核消失或固缩深染。与模型组比较,钩藤天麻药对高、中剂量组及阳性对照组上述指标均显著降低(P<0.01),肝组织结构有部分正常,肝细胞坏死减少,胞核消失或碎裂减少甚至完好,未见炎症细胞浸润和脂肪变性。Western blot结果显示,钩藤天麻药对可以下调NF-κB和TLR4蛋白,上调Nrf2蛋白的表达。结论:钩藤天麻药对可以通过抑制NF-κB,TLR4和Nrf2信号通路,预防和治疗药物性肝损伤。
Objective To explore the effect and molecular mechanism of Uncaria rhynchophylla-Gastrodia elata herb-pair in the treatment of drug-induced liver injury caused by Tripterygium glycosides tablets through NF-κB/TLR4/Nrf2 signaling pathway.Methods Male SPF BALB/c mice were randomly divided into six groups,including three Uncaria rhynchophylla-Gastrodia elata herb-pairgroups(the doses were 8.125 g·kg^(-1) d^(-1)、16.250 g·kg^(-1)·d^(-1) and 32.500 g·kg^(-1)·d^(-1),respectively),the positive control group(silybin 0.480 g·kg^(-1)),the blank control group and the model group(Tripterygium glycosides 0.300 g·kg^(-1)).After the last administration for 24 h,the eyeballs were removed for blood collection,and the activities of ALT and AST were determined.The liver was taken and the contents of glutathione,superoxide dismutase and malondialdehyde were determined,and the contents of TNF-αand lipid peroxide were detected by Elisa.HE staining and Western blot were performed to detect the expression of NF-κB,TLR4 and Nrf2.Results Compared with the normal group,the levels of ALT,AST,SOD,MDA,GSH-Px,LPO and TNF-αin model group were significantly increased(P<0.01).The liver tissue structure was severely abnormal,and hepatocyte steatosis,nuclear disappearance or pyknosis were observed.Compared with the model group,the above indexes in the high-dose,medium-dose Uncaria rhynchophylla-Gastrodia elata herb-pair groups and the positive control group were significantly decreased(P<0.01).The liver tissue structure was partially normal,the necrosis of liver cells was reduced,the disappearance or fragmentation of nucleus was reduced or even intact,and there was no inflammatory cell infiltration and fatty degeneration.Western blot results showed that Uncaria rhynchophylla-Gastrodia elata herb-pair could down-regulate the expression of NF-κB,TLR4 and up-regulate the expression ofNrf2.Conclusion Uncaria rhynchophylla-Gastrodia elata herb-pair can prevent and treat DILIvia NF-κB,TLR4 and Nrf2 signaling pathways.
作者
庞婷
李俊萱
马留辉
王志豪
何欢
覃清霞
PANG Ting;LI Junxuan;MA Liuhui;WANG Zhihao;HE Huan;QIN Qingxia(Guangxi Agricultural Vocational University,Nanning 530007,China;Nanning Health School,Nanning 530028,China;Guangxi Baicao Zhenxing Agricultural Science and Technology Co.,Ltd,Yulin 537000,China)
出处
《中国民族民间医药》
2025年第10期34-39,共6页
Chinese Journal of Ethnomedicine and Ethnopharmacy
基金
国家自然科学资助基金项目(81360524)
2024年度广西高校中青年教师科研基础能力提升项目(2024KY1249)
2023年院级科学研究与技术开发项目(XKJ2346)。
关键词
药物性肝损伤
钩藤
天麻
护肝
分子机制
Drug-Induced Liver Injury
Uncaria Rhynchophylla
Gastrodia Elata
Liver Protection
Molecular Mechanism
