摘要Objective To explore the protective effects and underlying mechanisms of H2S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells.Methods Cell viability was evaluated using CCK-8 assay.Apoptosis was measured using flow cytometry.Reagent kits were used to detect carbonyl stress markers malondialdehyde,4-hydroxynonenal,thiobarbituric acid reactive substances,and protein carbonylation.Aldehyde-protein adduct formation and alcohol dehydrogenase,aldehyde dehydrogenase 2,aldo-keto reductase,nuclear factor E2-related factor 2(Nrf2),and cystathionine β-synthase(CBS)expression were determined using western blotting or real-time PCR.Sulforaphane(SFP)was used to activate Nrf2.RNA interference was used to inhibit CBS expression.Results GYY4137(an H2S donor)pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts.GYY4137 effectively restored the uranium-decreased Nrf2 expression,nuclear translocation,and ratio of nuclear to cytoplasmic Nrf2,accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes.The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS,Nrf2 activation,nuclear translocation,and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes.Simultaneously,CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels,apoptosis rates,and uranium-induced cell viability.Conclusion H2S induces Nrf2 activation and nuclear translocation,which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H2S axis.Simultaneously,the Nrf2-controlled CBS/H2S axis may at least partially promote Nrf2 activation and nuclear translocation.These events form a cycle-regulating mode through which H2S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.