| Part I Wnt/β-catenin signaling pathway mediates the protective effect of Shenmai injection on cerebral ischemia-reperfusion injury in ratsAim To determine the Wnt/β-catenin signaling pathway mediates the protective effect of Shenmai injection(SM)on cerebral ischemia-reperfusion injury(CIRI)in rats.Methods According to the randomized block principle,84 SD rats were divided into 7 groups: sham operation group(sham),model group(MCAO),SM+model group(SM+MCAO),normal saline(NS)+model group(NS+MCAO),phosphate buffered solution(PBS)+SM+model group(PBS+SM+MCAO),Wnt/β-catenin antagonist dickkopf-1(Dkk-1)+SM+model group(Dkk-1+SM+MCAO),Dkk-1+model group(Dkk-1+MCAO),12 rats in each group.Rat CIRI model was established by middle cerebral artery occlusion(MCAO)with line embolus.Immediately after cerebral ischemia,SM+MCAO group,PBS+SM+MCAO group and Dkk-1+SM+MCAO group were intraperitoneally injected with SM(15 m L/kg),whereas NS+MCAO group was injected with equal amount of NS.At 30 min before the model was set up,Dkk-1+SM+MCAO group and Dkk-1+MCAO group were injected with Dk K-1(1g/L,1μL)to the ventricle,whereas PBS+SM+MCAO group was injected with equal amount of PBS.After reperfusion for 24 h,neurobehavioral score was assessed in each group,cerebral infarction volume was measured,expressions of Bcl-2,Bax and β-catenin protein were detected in the semi-dark zone of cerebral infarction,and Bcl-2/Bax ratio was calculated.Results Compared with the sham group,neurobehavioral score,cerebral infarction volume,and the expressions of Bcl-2,Bax,and β-catenin proteins were increased in the MCAO group(P<0.05),and Bcl-2/Bax ratio was reduced(P<0.05).Compared with the MCAO group,neurobehavioral score,cerebral infarction volume and Bax protein expression were significantly reduced in the SM + MCAO group(P < 0.05),the expressions of Bcl-2 and βcatenin proteins and Bcl-2/Bax ratio were significantly increased(P<0.05).Compared with the SM+MCAO group,neurobehavioral score,cerebral infarction volume and Bax protein expression were significantly increased in the Dkk-1+SM+MCAO group(P<0.05),while Bcl-2 protein expression and Bcl-2/Bax ratio were significantly decreased(P<0.05).Conclusion Shenmai injection improves brain damage of CIRI rat by up-regulation of Wnt/β-catenin signaling pathway.Part II Wnt/β-catenin Signaling Pathway improves rat cerebral ischemia-reperfusion injury by regulating autophagyAim:To observe the effect of Wnt /β-catenin signaling pathway on the autophagy level of cortical neurons in rats with cerebral ischemia-reperfusion.Methods: 56 SD rats(male)were divided into 4 groups randomly(n=14): one is the sham group,two is the cerebral ischemia-reperfusion group(group I/R),three is the Wnt signal pathway agonist Li Cl treatment group(Li Cl+I/R group),and four is the solvent group(NS+I/R group).The rat cerebral ischemia reperfusion injury model(middle cerebral artery occlusion,MCAO)was established by the occlusion of middle cerebral artery thread embolus.2H ischemia and reperfusion 24 h,the neurological deficit scores of Garcia change assessment neurobehavioral rats;the expression of β-catenin,LC3-II,P62 protein testing of rat cortex was measured by Western blot 24 h after reperfusion in rats.Results: 24 h after reperfusion,compared with group Sham,group I/R neurobehavior score decreased significantly(P < 0.05),the cerebral infarction volume was significantly increased(P < 0.05),the expression content of cortex beta-catenin decreased significantly(P < 0.05),the expression of LC3-II content in cortex increased significantly(P < 0.05),the level of p62 was significantly decreased(P<0.05);Li Cl+I/R group compared with I/R group,the neurological function scores were significantly higher(P < 0.05),the infarct volume was significantly reduced(P < 0.05),cortical beta-catenin expression increased(P < 0.05),cortical LC3-II decreased(P < 0.05),the level of p62 was significantly increased(P<0.05).Conclusion: Wnt/β-catenin signaling pathway can improve the nerve injury after focal cerebral ischemia and reperfusion in rats by regulating autophagy. |
