Objective:To investigate the protective effects of Schisandra chinensis oil(SCEO)against aristolochic acid Ⅰ(AAⅠ)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism.Methods:C57BL/6 mice were randomly divided into 5 groups according to a random number table,including control group,AA Ⅰ group,and AA Ⅰ+SCEO(0.25,0.5 and 1 g/kg)groups(n=5 per group).Pretreatment with SCEO was done for 2 days by oral administration,while the control and AA Ⅰ groups were treated with sodium carboxymethyl cellulose.Mice of all groups except for the control group were injected intraperitoneally with AA Ⅰ(5 mg/kg)from day 3 until day 7.Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling(TUNEL)staining,respectively.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),and serum creatinine(SCr),as well as renal malondialdehyde(MDA),glutathione,r-glutamyl cysteingl+glycine(GSH),and superoxide dismutase(SOD)were analyzed using enzyme-linked immunosorbent assay(ELISA).Expressions of hepatic cytochrome P450 1A1(CYP1A1),CYP1A2,and nad(p)hquinonedehydrogenase1(NQO1)were analyzed using ELISA,quantitative real-time polymerase chain reaction(qPCR)and Western blot,respectively.In vitro,SCEO(40 μ g/mL)was added 12 h before treatment with AA Ⅰ(40 μ mol/mL for 48 h)in human renal proximal tubule cell line(HK-2),then apoptosis and reactive oxygen species(ROS)were analyzed by flow cytometry.Results:SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL+ staining in the kidney tissues of mice with AA Ⅰ-induced nephrotoxicity,and reduced serum levels of ALT,AST,BUN and SCr(P＜0.01 or P＜0.05).SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney,containing MDA,GSH and SOD(P＜0.01 or P＜0.05).SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues(P＜0.01 or P＜0.05).Besides,in vitro studies also demonstrated that SCEO 40 μg/mL inhibited apoptosis and ROS generation(P＜0.05 or P＜0.01).Conclusions:SCEO can alleviate AA Ⅰ-induced kidney damage both in vivo and in vitro.The protective mechanism may be closely related to the regulation of metabolic enzymes,thereby inhibiting apoptosis and ROS production.

YANG Yan;GE Fei-lin;ZHAN Xiao-yan;MU Wen-qing;LI Zhi-yong;LIN Li;WEI Zi-ying;BAI Zhao-fang;SUN Qin;XIAO Xiao-he

School of Integrated Traditional Chinese and Western Medicine,Southwest Medical University,Luzhou,Sichuan Province,646000,China;Senior Department of Hepatology,the Fifth Medical Center of PLA General Hospital,Beijing,100039,China;China Military Institute of Chinese Materia,the Fifth Medical Center of PLA General Hospital,Beijing,100039,China

中国结合医学杂志（英文版）

[1]YANG Yan;GE Fei-lin;ZHAN Xiao-yan;MU Wen-qing;LI Zhi-yong;LIN Li;WEI Zi-ying;BAI Zhao-fang;SUN Qin;XIAO Xiao-he-.Schisandra chinensis Oil Attenuates Aristolochic Acid Ⅰ-Induced Nephrotoxicity in vivo and in vitro)[J].中国结合医学杂志（英文版）,2022(07):603-611

Aristolochic,Nephrotoxicity,SCEO,+SCEO,cysteingl+glycine,nad,hquinonedehydrogenase1,TUNEL+

Schisandra,chinensis,Oil,Attenuates,Acid,Induced,vivo,vitro,Objective,To,investigate,protective,effects,oil,against,aristolochic,acid,AA,induced,nephrotoxicity,elucidate,underlying,mechanism,Methods,C57BL,mice,were,randomly,divided,into,groups,according,number,table,including,control,Pretreatment,was,done,days,oral,administration,while,treated,sodium,carboxymethyl,cellulose,Mice,except,injected,intraperitoneally,from,until,Histopathological,examination,apoptosis,kidney,observed,hematoxylin,eosin,TdT,mediated,dUTP,nick,end,labeling,staining,respectively,levels,serum,alanine,aminotransferase,ALT,aspartate,AST,blood,urea,nitrogen,BUN,creatinine,SCr,well,renal,malondialdehyde,glutathione,glutamyl,GSH,superoxide,dismutase,analyzed,using,linked,immunosorbent,assay,Expressions,hepatic,cytochrome,P450,CYP1A1,CYP1A2,NQO1,quantitative,real,polymerase,chain,reaction,qPCR,blot,added,before,human,proximal,tubule,line,HK,then,reactive,oxygen,species,ROS,flow,cytometry,Results,ameliorated,histopathological,changes,tissues,reduced,alleviated,generation,containing,increased,expressions,decreased,liver,Besides,studies,also,demonstrated,that,inhibited,Conclusions,can,damage,both,may,closely,related,regulation,metabolic,enzymes,thereby,inhibiting,production

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