Effect of total glucosides of paeony on hepatic ischemia-reperfusion injury in rats by regulating RhoA/ROCK1 signaling pathway
Objective To investigate the effect of total glucosides of paeony on hepatic ischemia-reperfusion injury in rats by regulating RhoA/Rock1 signaling pathway.Methods The rat model with hepatic ischemia-reperfusion injury was established by blocking hepatic artery and portal vein for 1 h.And the sham operation group,model group,total glucosides of paeony(100 mg/kg)group,total glucosides of paeony+TGP(100 mg/kg+40 mg/kg)group,and total glucosides of paeony+LPA(100 mg/kg+1 mg/kg)group were set up,with 8 rats in each group.After 6 weeks of continuous treatment,the level of ALT,AST,TBiL in serum were measured,the hepatic tissue pathological changes and cell apoptosis were observed through HE or TUNEL staining,the hepatic injury score and apoptosis index(AI)were calculated.The oxidative stress indexes(SOD,CAT,and the content of MDA)in hepatic tissue were detected by spectrophotometer.The level of inflammatory factors(IL-1β,IL-6,TNF-α)were detected by ELISA method.The mRNA and protein expressions of RhoA,ROCK1,NF-κB p65,Bcl-2,Bax,C-Caspase-3 were in hepatic tissue were detected by reverse transcription-polymerase chain reaction(RT-PCR)or Western blotting.Results Compared with model group,the level of ALT,AST,TBiL in serum of total glucosides of paeony group and total glucosides of paeony+Rhosin group were significantly decreased(P<0.05).The pathological changes and cell apoptosis of hepatic tissue were significantly improved,the hepatic injury score and AI were significantly decreased(P<0.05).The activity of SOD,CAT were significantly increased,and the content of MDA,IL-1β,IL-6,TNF-α were significantly decreased(P<0.05).The mRNA and protein expression of RhoA,ROCK1,NF-κB p65,Bax,C-Caspase-3 were significantly decreased,while the mRNA and protein expression of Bcl-2 were significantly increased(P<0.05).Compared with total glucosides of paeony group,Rhosin could significantly enhance the effect of total glucosides of paeony on hepatic function,hepatic lesion,apoptosis,oxidative stress,inflammation,the expression of RhoA/ROCK1 signaling pathway-related mRNA and protein in HIR rats,while LPA could reversed the regulatory effect.Conclusion Total glucosides of paeony can alleviate oxidative stress,inflammation,cell apoptosis by inhibiting the RhoA/ROCK1 signaling pathway,thus playing a certain protective role against hepatic ischemia-reperfusion injury in rats.
total glucosides of paeonyhepatic ischemia-reperfusionRhoA/ROCK1 signaling pathwayapoptosisoxidative stress
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