【中图分类号】R285.5 【文献标志码】A 【文章编号】1007-8517（2025）10-0034-06

DOI： 10.3969/j .issn.1007-8517.2025.10. zgmzmjyzz202510007

Effect and Mechanism of Uncaria Rhynchophylla -Gastrodia ElataHerb -Pair on Drug-Induced Liver Injury Based on NF-κB/μLR4/νNrf2 Signaling Pathway

PANG Ting1LI Junxuan²MA Liuhui1WANG Zhihao³HE Huan1QIN Qingxia1* 1.Guangxi Agricultural Vocational University，Nanning 530o07，China；2.Nanning HealthSchol，Nanning 530028，China; 3.Guangxi Baicao Zhenxing Agricultural Science and Technology Co.，Ltd，Yulin 537Ooo，China

Abstract：Objective Toexplore theefectandmolecularmechanismof Uncariarhynchophylla-Gastrodiaelata herb-pair inthe treatment of drug-induced liver injury caused by Tripterygium glycosides tablets through NF-κB/ΩTLR4/ΩNrf2 signaling pathway. MethodsMale SPFBALB/c mice wererandomlydivided intosix groups，including threeUncariarhynchophyll-Gastrodia elata herb - pairgroups （ the doses were 8.12 5g⋅kg^-1d^-1 and 32.500g⋅kg^-1⋅d^-1 ，respectively），the positive control group （silybin 0.480g⋅kg^-1 ），the blank control group and the model group（Tripterygium glycosides 0.300g⋅kg^-1 ）. After the last administration for ^24h ，the eyeballs were removed for blood collection，and the activities of ALTand AST were determined.Teliverwas takenandthecontentsof glutathione，superoxidedismutaseandmalondialdehydeweredetermined，andthe contents of TNF-α and 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- α in model group were significantly increased（ Plt;0.01 ）.The liver tissue structure was severely abnormal，and hepatocytesteatosis，nucleardisappearanceor pyknosis wereobserved.Comparedwiththemodelgroup，theaboveindexes inthehighdose，medium-doseUncariarhynchophylla-Gastrodiaelataherb-pairgroupsandthepositivecontrol groupweresignificantlydecreased （ Plt;0.01 ）.The liver tissue structure was partially normal，the necrosis of liver cells was reduced，the disappearance or fragmentationofucleuswasreducedorevenintact，andterewasnoinflammatorycellinfitrationandfatydegenerationWestern blotresultsshowedthatUncariarhynchophll-Gastrodiaelataherb-paircoulddown－regulate theexpresionofNF-kB，TLR4 andup-regulatetheexpresionofNf2.ConclusionUncariarhynchophylla-Gastrodiaelataherb-paircanpreventandtreat DLIvia NF-κB ，TLR4 and Nrf2 signaling pathways.

Key Words：Drug-InducedLiver Injury； Uncaria Rhynchophyll;；Gastrodia Elata;Liver Protection； Molecular Mechanism

药物性的肝损伤（drug-induced liver injury，DILI），是一种在使用治疗剂量药物时，肝脏受到药物或药物代谢过程中所产生的代谢产物导致的毒性损伤或发生过敏反应所导致的肝脏损伤性疾病[1-2]。中药具有副作用小，多成分、多靶点的优点，是补充和替代医学的重要组成部分，也越来越受到国内外人们的重视。根据经典平肝方“天麻钩藤汤”（《小儿卫生总微论方》卷五）可知，君药钩藤、天麻均入肝经，具有平肝清热之功效，且对肝损伤导致的氧化应激、免疫应答及炎症反应有抑制作用。钩藤［Uncariarhynchophylla（Miq.）Miq.exHavil.]，为茜草科钩藤属带钩干燥茎枝，为广西道地药材之一，具有清热平肝、息风定惊功效。研究3表明，钩藤碱、槲皮素和山奈酚是钩藤的有效组分之一，其中槲皮素具有抗炎、抗氧化、清除自由基的作用，为酪氨酸蛋白激酶抑制剂，是最常见的黄酮化合物之一。在氧自由基造成的肝损伤中，槲皮素具有显著的治疗与保护作用[4]。天麻（Gastrodia elataBl.），兰科天麻属根茎，可用于治疗头晕目眩、肢体麻木、小儿惊风等。天麻中的天麻素（Gastrodin），具有增加动脉血管顺应性、降低外周血管阻力、改善心脑血管血流量、保护神经细胞、促进心肌细胞能量代谢的功能，同时具有护肝、清除自由基、增强免疫等作用[5]。而 NF-κB 、TLR4 和 Nrf2蛋白均为经典的调控肝损伤作用的蛋白，因此，钩藤天麻药对在治疗DILI时是否可以通过该通路发挥作用具有一定的研究意义，同时研究也为钩藤天麻药对在治疗DILI时的功效组分是否为槲皮素、山奈酚、天麻素以及后期代谢组学等奠定基础。……