基于Nrf2调控通路探讨鼠尾草酸对黄药子肝损伤的减毒作用机制

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【Abstract】Objective To investigate thedetoxification effect ofcarnosic acid（CA），a natural phenolic acid compound， onliverinjury inducedbyRhizoma DioscoreaeBulbiferaeandtoexplore itspotentialmechanism.MethodsMale KMmice were randomly divided into 6 groups （ n=8 per group）： control group （ 0.5% CMC-Na solution），model group （ethanol extract of Rhizoma Dioscoreae Bulbiferae）， silymarin group （silymarin + ethanol extract of Rhizoma Dioscoreae Bulbiferae），and low-， medium-， and high-dose CA groups （different doses of CA + ethanol extract of Rhizoma Dioscoreae Bulbiferae）.The micewere intragastricallyadministeredfo14consecutivedays，and theirfoodintake，water intakeandbody weight wererecorded.Afterthe endof the experiment，body weight andliver massof the mice were weighed，andliver index wascalculated.Theexpreion levelsof plasmaaspatate ainotrasferase （AT）lanieamnotransferase （AL），alkaieposphatase （L），totalbin （T-BIL），superoxide dismutase （SOD） activity，catalase （CAT），glutathione （GSH），and malondialdehyde （MDA）were determined.Westeblotingasusedtodetecttheprotenexpreionofnuclarfactoreryhrod2-relatedfactor2（rf2），eme oxygenase-1 （HO-1）， tumor necrosis factor- ∇⋅a （TNF-α），and interleukin-6 （IL-6）. Real-time quantitative polymerase chain reaction （RT-qPCR） was performed todeterminethemRNA expression ofmultidrug resistance-assciated protein 2 （MRP2），bilesalt export pump （BSEP），and uridine diphosphate glucuronosyltransferase1A1 （UGT1A1）. Hematoxylin-eosin （HE） staining was usedtoobserve thehistopathologicalchangesoflivertissues.ResultsComparedwiththemodelgroup，CAreducedliverweight and liver index inmice，decreasedplasma levels ofAST，ALT，ALP，andTBL，increasedplasmalevels ofSOD，CAT，adGH， and decreasedMDA levels.Itupregulatedtheprotein expressionofNuc-Nrf2and HO-1，inhibitedthe proteinexpressonofp-NFKB p65，TNF- ∇⋅a ，and IL-6， and promoted increases in the mRNA expression of MRP2， P-gp， BSEP，and UGT1Al （all P<0.05 ） The results of HE staining showed that CA reduced inflammatory infiltration and necrosis of hepatocytes and ameliorated hepatocellular structural damage. Conclusion CAmay exertadetoxificationefect against Rhizoma Dioscoreae Bulbiferaeinduced liver injury by activating the Nrf2 regulatory pathway and its downstream key indicators.

【Key words】 Carnosic acid; Rhizoma Dioscoreae Bulbiferae; Nrf2 regulatory pathway; Detoxification; Liver injury

随着中药在全球范围的广泛应用及药品不良反应监测体系的不断完善，因服用中药而导致不良反应的病例报道日渐增多，尤其以肝脏损伤较为突出［1］。（剩余17573字）