Effects Of Ginsenoside Rg1 On P38MAPK/NF-κBp65 Pathway In Rats With Cerebral Ischemia-reperfusion Injury

ObjectiveTo investigate the effect and mechanism of ginsenoside Rg1(GS-Rg1)on P38MAPK/NF-κBp65 inflammation-related pathway after focal cerebral ischemia-reperfusion injury(CIRI)in rats.MethodsSD rats were randomly divided into five groups: sham operation group,model group,GS-Rg1 low,medium and high dose group,13 rats in each group.Except for the sham operation group,the other groups were treated with middle cerebral artery embolization(MCAO)to prepare a focal cerebral ischemia reperfusion model.Before the model is made,it is continuously administered for 7 days,once a day,intraperitoneally,GS-Rg1 low dose group was given 10mg/kg,GS-Rg1 medium dose group was given at 20mg/kg,GS-Rg1 high dose group was given at 40mg/kg.Sham operation group and model group give an equal amount of saline.Postoperatively,neurobehavioral scores,TTC staining,and cerebral edema were used to determine whether the model was successful.ELISA was used to detect the expression of IL-1β and IL-6 in serum,and the expression of p38MAPK/NF-κBp65 pathway related factors was detected by immunofluorescence and Western blotting.ResultsCompared with the sham operation group,each group had varying degrees of neurological deficit symptoms,cerebral infarction and cerebral edema(P<0.01);compared with the model group,GS-Rg1 rats in each dose group had brain deficits Post-blood neurological deficit symptoms,cerebral infarction,and cerebral edema were significantly reduced(P < 0.05);compared with the low-dose GS-Rg1 group,the neurological deficit symptoms,cerebral infarction,and cerebral edema in the high-dose GS-Rg1 group were significantly lower than those in the low-dose group(P < 0.05),but there was no significant difference between the middle and high dose groups(P>0.05).Compared with the sham operation group,the expression levels of IL-1β and IL-6 in the model group and each medication group were significantly increased(P < 0.05).Compared with the model group,the serum IL-1β and IL-6 levels in each medication group were significantly higher.Significantly reduced(P < 0.01).Compared with the low-dose GS-Rg1 group,the serum IL-6 levels in the medium-and high-dose groups of GS-Rg1 were significantly reduced(P<0.05).But there was no significant difference between the medium-and high-dose groups(P>0.05).The results of immunofluorescence showed that the number of positive cells in the sham operation group was less than that in the model group,and the number of positive cells in the model group was significantly reduced.The results of immunoblotting showed that there were obvious expression bands of phos-p38 and phos-NF-κBp65 in the brain tissue of each group.Compared with the sham operation group,the expression levels of phos-p38 and phos-NF-κBp65 in the model group were significantly increased(P<0.01).Compared with the model group,the expression levels of phos-p38 and phos-NF-κBp65 in each treatment group decreased significantly(P<0.01).However,no significant difference was found in the expression level of phos-p38 between the treatment groups(P > 0.05).Compared with GS-Rg1 low-dose group,the expression level of phos-NF-κBp65 in the middle and high dose groups was significantly reduced(P<0.05).But there was no significant difference between the middle and high dose groups(P>0.05).Conclusion1.The inflammatory response is involved in the pathophysiology of CIRI.2.GS-Rg1 has neuroprotective effect on CIRI,and its mechanism may be inhibiting the expression of inflammatory factors IL-1β and IL-6 and the activation of P38 MAPK /NF-κBp65 pathway.