The Effects Of Pep2-8 Trifluoroacetate Salt On Focal Cerebral Ischemia/Reperfusion Injury By Regulating TLR4/NF-κB Signaling Pathway In Rat

Objective:Using Suture-occuluded method to establish transient middle cerebral artery occlusion(tMCAO)model in SD rat.Pep2-8 trifluoroacetate salt solution was administered by intraperitoneal injection to inhibit PCSK9 expression in rat.Using mathods,like IHC and Western Blot etc,to study the mechanism of neural protective effect on cerebral ischemic reperfusion injury,which Pep2-8 trifluoroacetate affected,by detecting TLR4,NF-κB,p38 MAPK expression.Methods:There were 120 healthy male Sprague-Dawley rats(250-300 g),that were averagely divided into 4 groups: sham operation group(30 rats),model group(30 rats),PCSK9 inhibitor low-dose group(30 rats),and PCSK9 inhibitor high-dose group(30 rats).Every groups were establish tMCAO model using Suture-occuluded method.With one exception.Sham operation group only find the CCA,ECA,ICA,no Suture-occuluded method using.After 1 hour of occlusion,reperfusion was achieved by withdrawing the suture to restore blood supply to the MCA territory.Infarct volume and BWC were measured at 24 h after reperfusion by TTC staining using image analysis software and wet/dry weight method.Using methods,like IHC and Western Blot etc,to detecting TLR4,NF-κB,p38 MAPK expression of brain tissue at 24 h after reperfusion.Results:1.Compared with the sham-operated group,the others have higher neurological deficit score.High dose PCSK9 inhibitor group has lower neurological deficit score than Low dose group(P<0.05).2.Shan operated group doesn’t have infarction compared others.There was significantly difference among I/R group,Low dose PCSK9 inhibitor group,High dose PCSK9 inhibitor group(P<0.05)at the volume brain infarction.3.There was significantly difference among I/R group,Low dose PCSK9 inhibitor group,High dose PCSK9 inhibitor group at the brain water content infarction(P<0.05).4.Compared with the sham-operated group,TLR4,NF-κ B,p38 MAPK expression are incrasing at 24 h after reperfusion(P < 0.05).Also,High dose PCSK9 inhibitor group has lesser expression of TLR4,NF-κ B,p38 MAPK than Low dose group(P<0.05).Conclusion:PCSK9 inhibitor Pep2-8 trifluoroacetate salt can improve neurological deficiency and reduce brain infarction volume after reperfusion in rat.The potential mechanism is PCSK9 inhibitor overrides TLR-4/NF-κB signaling pathway to reduce inflammation in early stage of CIRI.