The Effect Of Probucol Preconditioning On The Expression Of NF-?B And ICAM-1 After Cerebral Ischemia-reperfusion In Hyperlipidemia Rats

Objective: To observe the expression of nuclear factor kappa B(NF-?B)and cellular cell adhesion molecule-1(ICAM-1)in hyperlipidemia rats after cerebral ischemia-reperfusion by probucol pretreatment,and investigate the neuroprotection effect of probucol on brain tissue after cerebral ischemic-reperfusion in hyperlipidemia rats and the possible mechanism.Methods: 1.The establishment of Hyperlipidemia rat Model: 130 male SD rats were randomly divided into general Group(10)and high Fat Group(120),and the rats with hyperlipidemia were randomly divided into 4 groups,each group with 30: Sham operation group,ischemia-reperfusion group,low-dose probucol group,high-dose probucol group.Each group was divided into five subgroups according to 6h,12 h,24h,48 h and 72 h after ischemia,and 5 rats in each subgroup were added to each group.The infarct volume was calculated by TTC staining at 24 h after reperfusion for 2h after ischemia.The low dose and high dose probucol group were treated with 100mg/kg and 500mg/kg every day for 2weeks.The sham operation group and the ischemia-reperfusion group were given the same dose of 0.5%CMC.The middle cerebral artery occlusion(MCAO)model was made by the modified Longa method.3.Test indicators:The content of TC?TG?HDL-C?LDL-C,the pathological changes of brain tissue were observed by HE staining,the volume of cerebral infarction was calculated by TTC staining,the expression of NF-?B and ICAM-1 positive cells were detected by immunohistochemistry,and the expression of apoptotic cells was measured by tunel method.Results: 1.Hyperlipidemia model:Compared with the normal group,the contents of TC,TG and LDL-C inthe hyperlipidemia group increased and the content of HDL-C decreased,the difference was statistically significant(P<0.05).2.Neurological function score:Compared with the sham operation group,the neurological deficit score of 6h-72 h in the other groups was significantly lower(P<0.05),and the lowest at 24h-48 h.Compared with the ischemia-reperfusion group,the neurological deficit score of the low and high dose Probucol groups at 12h-72 h increased after operation(P<0.05).Compared with the low dose probucol group,the neurological deficit score of high dose Probucol groups at 12h-72 h increased after operation(P<0.05).3.Pathological changes of ischemic brain tissue: No pathological changes were found in the sham operation group.The pathological changes in the low-dose and high-dose Probucol groups were less than those in the ischemia-reperfusion group,especially in the high-dose group.4.Measurement of cerebral infarction volume ratio: No infarct was found in sham-operation group,but obvious infarct was found in ischemia-reperfusion group.Compared with ischemia-reperfusion group,the infarct volume ratio of low-dose and high-dose Probucol group was smaller(P<0.05).Compared with low-dose probucol group,the infarct volume ratio of high-dose Probucol group was smaller(P<0.05).5.The expression of NF-?b: Sham surgery group only a few NF-?b positive cells,the NF-?b positive cells of remaining groups began to increase from reperfusion 6h,12 h hours continued to increase,24 h to peak,48h-72 h decline,compared with sham surgery group,The difference was statistically significant(P<0.05).Compared with the ischemia-reperfusion group,The expression of NF-?b in brain tissue of low and high dose probucol decreased(P<0.05)in 12h-72 h,and the expression of NF-?b in high dose probucol decreased in 12h-72 h compared with low-dose probucol(P<0.05).6.The expression of ICAM-1: Sham surgery group only a few ICAM-1 positive cells,the ICAM-1 positive cells of remaining groups began to increase from reperfusion 6h,12h-24 h hours continued to increase,48 h to peak,72 h decline,compared with sham surgery group,The difference was statistically significant(P<0.05).Compared with the ischemia-reperfusion group,the expression of ICAM-1 in brain tissue of low and high dose probucol decreased(P<0.05)in6h-72 h,and the expression of ICAM-1 in high dose probucol decreased in12h-72 h compared with low-dose probucol(P<0.05).7.The expression of apoptotic cells : Sham surgery group only a few apoptotic cells,the apoptotic cells of remaining groups began to increase from reperfusion 6h,12h-24 h hours continued to increase,48 h to peak,72 h decline,compared with sham surgery group,The difference was statistically significant(P<0.05).Compared with the ischemia-reperfusion group,The expression of apoptotic cells in brain tissue of low and high dose probucol decreased(P<0.05)in 12h-72 h,and the expression of brain tissue apoptotic cells in high dose probucol decreased in12h-72 h compared with low-dose probucol(P<0.05).Conclusion: 1.On the basis of hyperlipidemia rat model,the model of rat middle cerebral artery ischemia-reperfusion can be more in line with the pathophysiological mechanism of human cerebral ischemia-reperfusion.2.Probucol pretreatment can improve the neurological function defect,reduce the volume of cerebral infarction and apoptosis,and then alleviate the brain injury in hyperlipidemic rats,especially in high dose.3.After cerebral ischemia-reperfusion,the expression of NF-kappa B plays an important role in promoting cell apoptosis.Decreasing the expression of NF-kappaB and inhibiting neuronal apoptosis may be the mechanism of protective effect of probucol pretreatment on brain.4.After cerebral ischemia reperfusion,the expression of NF-kappaB and ICAM-1 plays an important role in promoting the inflammatory reaction,reducing the expression of ICAM-1 and NF-kappaB and thereby reducing the inflammatory reaction after cerebral ischemic reperfusion may be the mechanism of protective effect of probucol pretreatment on brain.