抑制铁死亡减轻敌草快引起的斑马鱼急性肾损伤的机制
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Inhibition of ferroptosis alleviates acute kidney injury caused by diquat in zebrafish
OUZejinl²，ing，HENSh，WANGZiyi，Heiyi，HENZhicheng，NGhihao2，ENGXiaojing，G Zhi1，2 （202 KeyLaboratoailetteftlessitaloie Occupationoetallthgodicalesityanua;lofublclt MedicalUeityaguin;holblicalthorthianedicalegeco
Abstract：ObjectiveToinvestigatetheroleofferoptosisindiquat-inducedacutekidneyinjury（AKI）anditsmolecular mechanisms.MethodsTransgeniczebrafishmodelswithTg（Eco.Tshb：EGFP）labelingoftherenaltubulesandTg（lyz：dsRed2） labeling of theneutrophils werebothdivided intocontrolgroup，gentamicin （positivecontrol） group，diquatpoisoninggroup， feroptosis inibitorgroup.Theindicatorsofidneyinjuryinflammatoryresponse，andferoptosis wereexaminedinthe zebrafish，andthecangesinexpressionsofvotagedependentanon-selectivecaelprotein1（VDAC1）anditohodial feritin（FTMT）weredetectedusingWesternbloting.ResultsAKIinducedbydiquatexhibitedasignificantdose-ffect relationship，and the severityof injury was proportional tothe exposureconcentration.Diquat alsocaused marked oxidative stressand inflammatoryresponses in the zebrafish models.Rhodamine metabolism assyand HE staining revealed significantlydeclinedglomerularfiltrationfunctionofthezebrafishasdiquat exposureconcentration increased. Immunofluorescence staining highlighted significantchanges in the expressionsofferoptosis markers GPX4andFTH1 in zebrafishrenal tissues followingdiquat exposure.Indiquat-exposed zebrafish，treatment with ferrostatin-1，afotosis inhibitor，obviouslyupregulatedGPX4anddownregulatedFTH1expressionsandimprovedthemetabolicateofglucan labeled withrhodamineB.Diquat exposure significantlyupregulatedtheexpressionofVDAC1andFTMTinzebrafish，and theapplicationof ferrostatin-1and VBIT-12 （a VDAC1 inhibitor） bothcausedpronounced downregulationofFTMT expression.ConclusionFeroptosisisacriticalmechanismunderlyingdiquat-inducedAKI，inwhich VDAC1andFplay important regulatory roles， suggesting their potential as therapeutic target for AKI caused by diquat.
Keywords：diquat;acutekidneyinjury;ferroptosis;voltage-ependenanion-selectivechannelprotein1;mitochondlitin
临床上，急性敌草快中毒能够引起肾、肝和肺等多个器官功能严重损伤，是其主要的致死原因[1-3]。（剩余15301字）
