The Effect Of JianNaoAn On Excessive Glucocorticoid Causing Neuronal Apoptosis In Hippocampus Induced By Cerebral Ischemia-reperfusion

Stroke is one of three important diseases threaten healthy of human being. Ischemia stroke withhigh mortality rate and disabilities rate is accout for 55%～80% of stroke. Cerebral ischemiareperfusion injury is one mainly pathological mechanism of ischemia stroke. The functionaldisturbance of the network of neuro-endocrine and immune (NEI) induced by cerebral ischemiareperfusion heighten abnormally glucocorticiod (GCS) in hippocampus and plasm ,and aggravatepathological impairment after cerebral ischemia reperfusion. Recently investigation showed thatexcessive GCS is one of important pathological factors causing neuron apoptosis in mayor brainregions such as hippocampus related with cognitive function, which is responsible for vasculardementia (VaD) after stroke. At present , the mechanism induced neuron apoptosis by higher GCS isremained unkown. JianNaoAn with function of BuShenHuoXueHuTan, is one effective compoundof Chinese herbal drug on curing VaD. The proceding experimental result has confirmed the functionof JianNaoAn down-modulated genes expression of IL-1,CRF related to NEI and relievedimpairment of nerve cells induced by cerebral ischemia –reperfusion. We investigate the action aboutexcessive GCS causing neurons apoptosis after cerebral ischemia and the influence of JiaNaoAn onthis pathological machenism through radioimmunoassay( RIA), immunohistochemistry, in situhybridization and TUNEL experimental techniques. Furthermore the protective function ofJianNaoAn on neuron after cerebral ischemia-reperfusion and potentially pharmacological methanismto prevent and cure post-stroke dementia were revealed. At2h,6h,12h,24hofischemia-reperfusiondifferentpoints,theconcentrationofcortisioloftheJiaNaoAn treated group in plasm and hippocampus decreased significantly compared with the modelgroup(P<0.05).Thenumberofpositivecellsisreducedsignificantlycompared with the model groupby TUNEL staining method, especially in reperfusion 12h,the distinction in number of positive cellbetween the JiaNaoAn treated group and the model group is very significant (P<0.01) . The proteinsand mRNA expression of NMDAR,cytochrome C and caspase 3, which are the key genes in theapoptosis pathway of dependent mitochondrion , are down-modulated in the treatment group and theantagonist group ,and there were distinct differencecompared with the modelgroup. However,there isno significant difference about the expression of glucocorticoid receptor between the treatment groupand the model group. By the apoptosis pathway of dependent mitochondrion that excessive GCScaused neurons apoptosis in hippocampus is confirmed in our experiment. But JianNaoAn can reduce英文摘要 -3-selectivelyGCSandinhibittheactivityoftheapoptosispathwayofdependentmitochondrioninducedby excessive GCS, and then decrease the degree of apoptosis in hippocampus after cerebral ischemia-reperfusion. The protective action is one function of preventing neurons from injury resulted fromcerebral ischemia-reperfusion. Meanwhile, the function of BuShenHuoXueHuaTan method onregulating the disturbance of network of NEI induced by cerebral ischemia-reperfusion may be animportant biological mechanismof protecting neurons, preventing and treating vascular dementia.