| 1.BackgroundCerebrovascular disease is harmful to the health of middle-aged and older for a class of diseases.As the population ages,the incidence of cerebrovascular disease rate increased year by year trend,China is the world's high incidence of cerebrovascular disease among the countries.According to statistics:In our country,there are 2,000,000 ~ 1,600,000 new cases of ischemic-stroke every year.80%of which have varying degrees of dysfunction, 50%~ 70%of which left over Varying degrees of cognitive impairment,about 25%of which develop into dementia.Each year which die from ischemic stroke in our country as many as 750,000 of the total stroke mortality 3 / 4,the disease has become a human health and the serious threat to quality of life. Finding effective means of treatment and to explain its mechanism is still the field of brain science research hot spots.Ischemic stroke was mainly due to regional cerebral circulatory disturbance caused by mental retardation,physical movement dysfunction as the main clinical manifestations of common diseases.Ischemic brain tissue can be divided into severe ischemia without reperfusion necrosis of the center is located in the surrounding areas and low-perfusion of ischemic penumbra (ischemic penumbra,IP).Surrounding penumbra brain electrical activity although the ceils tended to stop,but are still capable of maintaining transmembrane ion balance and the basic integrity of cell structure.With the extension of ischemic time,the gradual expansion of necrotic area,while the penumbra shrinking[1].Ischemic lesions in the brain areas,neuronal necrosis and apoptosis of co-existence of necrosis located in the central area of ischemia,apoptosis was seen in the ischemic penumbra,apoptosis may determine the final infarct volume.Therefore,as soon as possible ischemic penumbra function,resist apoptosis and rescue the damaged cells is the key to the treatment of cerebral ischemia.Apoptosis is activated by cellular genes,enzymes and signal transduction pathways regulating is a "waterfall" process in the active cell death process. Whether the nerve cell apoptosis in many cell activity is the result of a common factor.Among them,in particular,JAK(Janus kinase) / STAT(signal transducer and activator of transcription) family of control plays a decisive role in this.The current study found that:apoptosis may be related to STAT1 activation related to cell survival and repair may be associated with STAT3, STAT5 activation.Acupuncture in the treatment of cerebral ischemic disease has a unique effect.However,the intrinsic role of acupuncture mechanism is still not clear enough.Our research group in apoptosis,neural protective mechanisms,such as synaptic plasticity has done a great deal of research work,based on this study acupuncture intervention in a rat model of cerebral ischemia in the brain signal transduction systems,explore the lesions the region that the signal transduction system STAT family members and their mRNA expression levels and related factors modulation mechanism,a better understanding of acupuncture treatment for cerebral ischemia,interfere with the internal mechanisms of apoptosis,have a certain reference value.2.Experimental Study2.1 Electroacupuncture on focal cerebral ischemia model of learning and memory in ratsIn this study,among Morris water maze trial of behavioral indicators, electro-acupuncture testing the model of the time the improvement of learning and memory function,and through the creation of sham-operated group,model group and three sets of electro-acupuncture group compared to the role of electro-acupuncture treatment conduct a preliminary study.The results showed that:first,in the navigation experiment,pre-made model among the three groups was roughly the same average escape latency,no statistically significant(P＞0.05):after the model of two total average escape latency level three groups inter-compared to sham-operated group the lowest value, the second electro-acupuncture group,model group,the highest.Statistical analysis showed that:compared with the sham-operated group,model group were significantly different(P＜0.001),electro-acupuncture group was no significant difference(P＞0.05);Compared with model group,EA group was significantly less than the numerical low difference between the two groups was significant(P＜0.01).Second,test space exploration:in the former platform quadrant swim time for the first time through,40cm,Central time and 40cm piercing ring piercing the number of the four indicators,the model group and sham-operated group were significantly different(respectively P＜0.05,P＜0.05,P＜0.01,P＜0.01),prompted cerebral ischemic injury can lead to a lower level of learning and memory;electro-acupuncture group compared with the model group,the four indicators are significantly different (respectively P＜0.05,P＜0.05,P＜0.05,P＜0.01),but compared with the sham-operated group,the four indicators there was no significant difference (P＞0.05).The results suggest that cerebral ischemia model can reduce the level of learning and memory in rats,which can lead to cerebral ischemic injury model of decline in cognitive function in rats.And electro-acupuncture intervention can improve cerebral ischemic injury due to the decline in cognitive abilities,learning and memory in rats level.2.2 Electric model for focal cerebral ischemia in rat brain STAT1-positive neurons and the impact of the expression level of STAT1mRNACaused by cerebral ischemia in the local inflammatory response, JAKs-STATs signal transduction family of lesions apoptosis plays an important role in the process,in which STAT1 activation may be related to apoptosis-related.Thus,after cerebral ischemia in STAT1 signal transduction and its regulation and control mechanisms,as well as the role of electroacupuncture intervention,the understanding of electro-acupuncture therapy on cerebral ischemia in a certain intervention mechanism intrinsic significance.Methods:SD rats SPP level 90,male,weight 220±20g,by the random number table were randomly divided into sham operation group(J),model group (M) and EA group(Z),each group was divided into for 2 hours(h),24 hours (h),3 days(d) the three time period groups,a total of 9 groups,10 rats per group.Closed using electrocoagulation of middle cerebral artery induced by focal cerebral ischemia model sham surgery only in rats exposed to middle cerebral artery,no condensate closed.Electro-acupuncture group selected Baihui Du Meridian(GV20),Dazhui(GV14) two points to 1-inch filiform needles Puncture obliquely Baihui 0.5-inch,0.3-inch into the Dazhui,the two connected to electro-acupuncture points,with spacing Poland,5 ~ 10 times / s,the strength to quiet tolerance for rats,about 2 ~ 3V,time 30min,day 1.Z2h group one hour after the operation for the treatment of electro-acupuncture,electro-acupuncture for half an hour,half an hour after treatment were killed after perfusion fixation,Z24h group the same time the next day after the end of electro-acupuncture to deal with;Z3d group therapy for three days at the same time post-processing.Sham operation group and model group at corresponding time for processing.STAT1 Immunohistochemical, in situ hybridization to operate in strict accordance with the kit,were used to detect the lesion side of cortex,hippocampus CA1 area theaverage number of positive cells,with an average cross-sectional area,the average optical density.The results showed that:the model of the two hours group and sham operation indicators are quite two hours,no significant difference(P＞0.05).Model of a 24-hour group in addition to the expression of positive cells in the hippocampus STAT1mRNA the average optical density than the model group,fell slightly short of two hours,the other indicators were slightly higher than the model group of two hours.Suggest that cerebral ischemia after 24 hours after,STAT1 and the expression level of STAT1mRNA slight increase,but compared with the sham-operated group the increase was no significant difference(P＞0.05).Model group,group 3 days,lesions adjacent to the cortex and hippocampus of the STAT1-immunoreactive cells and mRNA expression of indicators of positive cells in all two hours with the model group, sham-operated group of 3 days were significantly more than the increase between the two comparison,the average cell count,the average cross-sectional area, the average optical density value of the three have significant difference (significant for P＜0.05 to P＜0.001).Tip:pathology in focal cerebral ischemia under the influence of cortex and hippocampus lesions inherent level of the third day of the beginning of a significant increase in STAT1. Electroacupuncture Electroacupuncture group two hours each indicator two hours with sham group,model two hours there was no significant difference between groups(P＞0.05);electro-acupuncture group targets a 24-hour than the electro-acupuncture group a slight increase in two hours,However,no significant difference,with the model of a 24-hour group and the sham-operated 24-hour group is also no significant difference(P＞0.05);electro-acupuncture group and 3 days of electroacupuncture group of two hours,a 24-hour electro-acupuncture group,in these indicators only slightly increased,but among non-statistically significant difference.Group comparison showed that the hippocampus in the lesion side and lesion side of the STAT1 level of the cortex,STAT1mRNA expression level,the average cell count,the average cross-sectional area,the average optical density value of the three indicators for three days with the sham-operated group,the numerical the difference was not obvious,statistically no significant difference.But three days with the model group,all indicators were significantly lower,both compared to the indicators have statistically significant difference (significant for P＜0.05 to P＜0.001).Conclusion:Electro-acupuncture therapy on cerebral ischemia-induced STAT1 levels,STAT1mRNA increase the expression level of a certain degree of inhibition.As a result of the increased STAT1-induced apoptosis may be a key factor in the signal,therefore,power for its inhibition may be to reduce the penumbra neuronal apoptosis,impaired brain function to improve an important way.2.3 Electric model for focal cerebral ischemia in rat brain STAT3-positive neurons and the impact of the expression level of STAT3mRNASTAT3 activation may be involved in cell anti-apoptotic signal transduction[3].Thus,STAT3 in the post-ischemic signal transduction, regulation and control mechanisms,as well as the role of electroacupuncture intervention,the understanding of electro-acupuncture treatment of cerebral ischemia in a certain intervention mechanism intrinsic significance. Second,the same experimental method.The results showed that:sham-operation among the three groups no significant changes in the indicators,the difference was not significant(P＞0.05).Model group,the model of two hours each indicator with the sham-operated group compared to two hours,there is a certain degree of increase;model of a further increase in 24-hour group.A number of indicators with a 24-hour sham operation group and model group compared to two hours, there was a significant difference(significant for P＜0.05 to P＜0.001).Model 3-day group,the indicators back to two hours with the model group level,the model was significantly lower than the 24-hour group.Statistically,the model group,model group and three days between 24-hour side of the cortex in the lesion-positive cells in the average cell count,the average cross-sectional area,the average optical density value of positive cells in hippocampal CA1 area of the average optical density and the expression of positive STAT3mRNA cortex cells in the lesions of the average cross-sectional area,hippocampus CA1 area ofpositive cells,such as indicators of the average cell count were significantly different(significant for P＜0.05 to P＜0.01).Three sets of electro-acupuncture group and model group also appeared similar to the changes began to increase at 2 hours,24 hours maximum,3 days reduced.However,three groups of electroacupuncture numerical indicators were higher than the corresponding numerical model group,with the model group than the 24-hour, 24-hour electro-acupuncture group were significantly higher indicators data.Statistics show:two in the lateral cortex lesions STAT3 positive cells in the immune cells on average,the average cross-sectional area,the average optical density,hippocampal CA1 area STAT3 positive cells in the immune cells, as well as the average STAT3mRNA expression of positive cells in the lateral cortex lesions The average cell count,the average optical density and the hippocampal CA1 area of the positive cells,such as indicators of the average cross-sectional area are significantly different(significant for P＜0.05 to P＜0.01).Electro-acupuncture group and 3 days compared to 3-day model,the data also have obvious advantages,including the side in the cortex lesions STAT3 immunoreactive cell average cross-sectional area and lateral lesions STAT3mRNA cortex cells to express the average number of positive cells,with an average cross-sectional area,the average light density values and the expression of hippocampal CA1 area STAT3mRNA average number of positive cells, such as indicators,both of which were significantly different(significant for P＜0.05 to P＜0.01).The results showed that:power STAT3mRNA for STAT3 expression levels and the increase in the level of a certain role,and a certain degree of continuity. Tip:power for the improvement of the role of brain function may be related to increaseof power for STAT3 to reduce the focus of apoptosis of nerve cells have a certain relationship.2.4 Electric model for focal cerebral ischemia in rat brain neurons STAT5 positive impactStudy found that STAT5(signal transducer and activator of transcription) in erythropoietin and erythropoietin receptor in the cell signal transduction pathway,In cerebral ischemia,can enhance neuronal resistance to ischemic hypoxia the ability of brain cells in order to play a local role in the protection.Therefore,the study of STAT5 in the brain after ischemia and the regulation of signal transduction mechanisms,as well as the role of electroacupuncture intervention,the understanding of electro-acupuncture therapy on cerebral ischemia in a certain intervention mechanism intrinsic significance. Second,the same experimental method.The results showed that:compared with the sham-operated group,model group,after 2 hours significantly increased the indicators,the highest value, lower value after 24 hours,a further reduction after 3 days,close to the level of sham-operated.One model in the two hours group lateral cortex lesions and hippocampal CA1 area the number of immunopositive cells in STAT5 two indicators with the sham operation 2 hours were significantly different(P＜0.05).Numerical changes in electro-acupuncture group and model group,the trend of a certain degree of similarity,that is,two hours each indicator increased significantly 24 hours after the beginning of some lower value,but some indicators have increased but,3 days after all the indicators are lower However,decrease was significantly lower than the model group.Compared with model group,EA group were higher than the data model of the corresponding set of indicators.Among them,electro-acupuncture group and two hours compared to model two hours,with the exception of lateral cortex lesions immunoreactive cells STAT5 average optical density,the other side of cortex lesions and hippocampal CA1 area of the indicators are statistically significant difference(significant for P＜0.05 to P＜0.01). Electro-acupuncture group and 3 days compared model 3 days,with the exception of lateral cortex lesions STATS average number of immunopositive cells,the other five indicators have three days with the model group were significantly different,are significant P＜0.05.The results suggest that:electro-acupuncture in cerebral ischemia can be markedly improved the early super-STAT5 levels,stimulate the body's self-protective mechanism at the same time,such a protection mechanism in the electro-acupuncture intervention can be extended to 3 days.Suggest that increases the level of STATS to stimulate STAT5 mediated by self-protection mechanism may be electro-acupuncture treatment of ischemic brain injury,one of the internal mechanism.3 Conclusion:To sum up:electro-acupuncture can improve the cerebral ischemia model in the level of learning and memory in rats,the ischemic brain injury on the function of improving the internal mechanism may be associated with ischemic lesions of Electroacupuncture on the district role in regulating STAT system has some relevance,that is,STAT1 inhibiting mRNA expression level and to enhance STAT3,STAT5 expression levels and STAT3mRNA.Formed in this way through the self-protection and repair mechanisms start to suppress lesion penumbra zone apoptosis,restoration of damaged brain cell function.Initial examinations of the "acupuncture stimulation - signal conditioning - from the start is the steady-state regulation of local cerebral ischemia in the key role of self-repair mechanism," the scientific hypothesis,for acupuncture treatment of ischemic cerebrovascular disease to provide a certain amount of scientific evidence and theoretical guidance.
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