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脑缺血后脑内STAT系统调控及电针干预作用的研究

Study on Regulation of STAT’s Signal-transduction System and the Acupuncture-intervention after Cerebral-ischemia

【作者】 于涛

【导师】 许能贵;

【作者基本信息】 广州中医药大学 , 针灸推拿学, 2009, 博士

【摘要】 1.背景资料脑血管疾病是危害中老年人健康的一类常见病。随着人口的老龄化,脑血管疾病的发病率有逐年增高的趋势,我国属于世界上脑血管疾病高发国家之一。据统计:在我国,每年仍有160万~200万脑缺血卒中新发病例。其中80%有不同程度的功能障碍,50%~70%遗留有轻重不等的认知障碍,约有25%发展成痴呆。每年我国死于缺血性卒中的人数高达75万,占全部中风病死亡率3/4,该病已经成为人类的健康和生存质量的严重威胁。因此寻找有效的治疗手段并阐释其机理仍然是目前脑科学领域的研究热点。缺血性中风主要是由于脑局部循环障碍,引起以智力障碍、躯体运动功能障碍为主要表现的临床常见疾病。缺血区的脑组织可分为严重缺血的无灌流的中心坏死区和位于周边的低灌流的缺血半暗带区(ischemic penumbra,IP)。周围的半暗带区脑组织虽然其细胞电活动趋于停止,但尚能维持离子跨膜的平衡和细胞结构的基本完整。随着缺血时间的延长,坏死区逐渐扩大,而半暗带区不断缩小。在脑缺血病灶区,神经元坏死与凋亡并存,细胞坏死位于缺血中心区,细胞凋亡主要出现在缺血半暗带,凋亡可能决定了最终梗死体积。因此,尽快恢复缺血半暗带的功能,抵制凋亡和抢救受损细胞是治疗脑缺血的关键。细胞凋亡是受细胞内活性基因,酶和信号转导途径调控的一个“瀑布式”过程,是细胞主动死亡的过程。神经细胞是否发生凋亡是许多细胞活性因子共同作用的结果。其中,尤其以JAK(Janus kinase)/STAT(signal transducer and activator oftranscription)家族的调控对此起着决定性的作用。目前研究发现:细胞凋亡可能与STAT1激活相关,而细胞生存和修复可能与STAT3、STAT5激活有关针灸在治疗脑缺血性疾病有独特的疗效。但针灸治疗的内在作用机制仍不太清楚。我们前期已经在细胞凋亡、神经保护机制、突触可塑性等方面作了大量的研究工作,在此基础上,研究针灸干预对脑缺血大鼠模型脑内信号转导系统的影响,探讨病灶区域内信号转导系统即STAT家族各成员及其mRNA表达水平及相关调制因子作用的机制,对进一步了解针灸治疗脑缺血,干预细胞凋亡的内在机制,有一定的参考价值。2.实验研究2.1电针对局灶性脑缺血模型大鼠学习记忆的影响本研究试用Morris水迷宫的行为学指标,检测电针在各时段治疗对该模型学习记忆障碍的改善作用,并通过设立假手术组、模型组和电针组三组相对照来对电针治疗作用的进行初步研究。结果显示:一、在定向航行试验中,造模型前,三组间平均逃避潜伏期大体相当,统计学上无显著性(P>0.05):造模后的两次总平总平均逃避潜伏期三组间相比较,假手术组数值最低,电针组第二,模型组最高。统计学分析显示:与假手术组相比,模型组有显著性差异(P<0.001),电针组无显著性差异(P>0.05):与模型组相比,电针组的数值明显较低,两组差异具有显著性(P<0.01)。二、空间探索试验中:在原平台象限游泳时间、第一次穿越时间、40cm环穿环时间和40cm环穿环次数四个指标,模型组与假手术组均有显著性差异(分别P<0.05,P<0.05,P<0.01,P<0.01),提示脑缺血损伤可以导致学习记忆水平的降低;电针组与模型组相比,四个指标均具有显著性差异(分别P<0.05,P<0.05,P<0.05,P<0.01),但与假手术组相比,四个指标差异无显著性(P>0.05)。结果提示,脑缺血造模可降低大鼠学习记忆水平,即脑缺血损伤可以导致模型大鼠的认知功能下降。而电针干预可以明显改善因脑缺血损伤下降的认知能力,提高模型大鼠的学习记忆水平。2.2电针对局灶性脑缺血模型大鼠脑内STAT1阳性神经元和STAT1mRNA表达水平的影响在脑缺血引起的局部炎性反应中,JAKs-STATs家族的信号传导对病灶区细胞凋亡过程起着重要的作用,其中STAT1激活可能与细胞凋亡相关。因此,研究STAT1在脑缺血后的信号转导及其调控机制以及电针的干预作用,对了解电针治疗对脑缺血的内在干预机制有着一定的意义。方法:将SPF级SD大鼠90只,雄性,体重220±20g,由随机数字表法随机分为假手术组(J)、模型组(M)和电针组(Z),每组又分为2小时(h)、24小时(h)、3天(d)三个时间段组,共9小组,每小组10只大鼠。采用的电凝闭大脑中动脉致局灶性脑缺血模型假手术者只做手术暴露大鼠大脑中动脉,不予凝闭。电针组选取督脉经穴百会(GV20)、大椎(GV14)两穴,以1寸毫针向后斜刺百会0.5寸,直刺大椎0.3寸,两穴接上电针,用疏密波,5~10次/s,强度以大鼠安静耐受为度,约2~3V,时间30min,每天1次。Z2h组在手术后一小时进行电针治疗,电针半小时,治疗后半小时后处死灌流固定、Z24h组治疗与Z2h组相同,在造模24小时后处理;Z3d组在同一时间治疗三天后处理。假手术组和模型组均在相应的时间进行处理。STAT1的免疫组化、原位杂交检测严格遵照试剂盒操作,分别检测病灶侧皮质、海马CA1区的阳性细胞平均个数、平均截面积、平均光密度值。结果显示:模型2小时组各指标均和假手术2小时相当,无显著性差异(P>0.05)。模型24小时组除海马STAT1mRNA表达阳性细胞的平均光密度比模型2小时组稍低外,其余指标均稍高于模型2小时组。提示,脑缺血后24小时后,STAT1和STAT1mRNA表达水平有轻微的增加,但与假手术组相比增加幅度无显著性差异(P>0.05)。模型组3天组,病灶侧皮质区和海马区的STAT1免疫阳性细胞和mRNA表达阳性细胞在所有指标上与模型2小时组、假手术3天组比均有显著的增加,两两者比较,在平均细胞数、平均截面积、平均光密度值三个方面均有显著性差异(显著性为P<0.05至P<0.001)。提示:在局灶性脑缺血病理影响下,病灶区皮质和海马内在第三天开始STAT1和mRNA表达水平均显著增加。电针组中电针2小时组各指标与假手术2小时组、模型2小时组间均无明显差异(P>0.05);电针24小时组各指标比电针2小时组稍有增加,但无显著性差异,与模型24小时组和假手术24小时组间也无显著性差异(P>0.05);电针3天组与电针2小时组、电针24小时组相比,在上述指标上仅有轻微地增高,但三者间在统计学上无显著性差异。组间比较显示,在病灶侧海马区和病灶侧皮质区的STAT1水平、STAT1mRNA表达水平上,平均细胞数、平均截面积、平均光密度值三个指标与假手术3天组相比,数值差别不明显,统计学上无显著性差异。但与模型3天组相比,所有指标均明显偏低,两者相较,各指标在统计学上有明显差异(显著性为P<0.05至P<0.001)。结论:电针治疗对脑缺血引发的STAT1水平、STAT1mRNA表达水平的升高有一定的抑制作用。由于STAT1的增高可能是诱导细胞凋亡的一个关键性的信号因素,因此,电针对其的抑制作用有可能是减少半暗带区神经细胞凋亡、改善受损脑功能的一个重要途径。2.3电针对局灶性脑缺血模型大鼠脑内STAT3阳性神经元和STAT3mRNA表达水平的影响STAT3激活可能参与细胞抗凋亡的信号转导。因此,研究STAT3在脑缺血后的信号转导、调控机制以及电针的干预作用,对了解电针治疗脑缺血的内在干预机制有着一定的意义。实验方法同实验二。结果显示:假手术三组间各指标无明显改变,差异不显著(P>0.05)。模型组中,模型2小时组各指标与假手术2小时组相比,均有一定程度的增加;模型24小时组进一步增加。多个指标与假手术24小时组和模型2小时组相比,差异有显著性(显著性为P<0.05至P<0.001)。模型3天组,各指标恢复到与模型2小时组的水平,明显低于模型24小时组。统计学上,模型组3天组与模型24小时两者在病灶侧皮质区阳性细胞平均细胞数、平均截面积、平均光密度值、海马CA1区阳性细胞的平均光密度值以及STAT3mRNA表达阳性细胞在病灶皮质区的平均截面积、海马CA1区的阳性细胞平均细胞数等指标均有显著性差异(显著性分别为P<0.05至P<0.01)。电针组三组也出现与模型组相类似的变化,2小时时开始升高,24小时最高,3天时降低。但电针三组各指标数值均高于相对应的模型组的数值,与模型24小时组比,电针24小时组各指标数据均明显偏高。统计学上显示:两者在病灶侧皮质区STAT3免疫阳性细胞平均细胞数、平均截面积、平均光密度值、海马CA1区STAT3免疫阳性细胞平均细胞数以及STAT3mRNA表达阳性细胞在病灶侧皮质区的平均细胞数、平均光密度值和海马CA1区的阳性细胞平均截面积等指标都有显著性差异(显著性分别为P<0.05至P<0.01)。电针3天组与模型3天组相比,数据也有明显优势,其中在病灶侧皮质区STAT3免疫阳性细胞平均截面积和病灶侧皮质区STAT3mRNA表达阳性细胞平均细胞数、平均截面积、平均光密度值和海马CA1区STAT3mRNA表达阳性细胞平均个数等指标上,两者均有显著性差异(显著性分别为P<0.05至P<0.01)。结果提示:电针对STAT3水平和STAT3mRNA表达水平有一定的上调作用,并有一定的持续性。提示:电针对脑功能的改善作用,可能与电针对STAT3上调,减少病灶区神经细胞的凋亡有一定的关系。2.4电针对局灶性脑缺血模型大鼠脑内STAT5阳性神经元的影响研究发现STAT5(信号转导和转录激活子)参与促红细胞生成素和促红细胞生成素受体的细胞信号转导途径。在脑缺血时,促红细胞生成素和促红细胞生成素受体的增加能提高缺血区神经元抵制缺氧的能力,从而起到对脑细胞的保护作用。因此,研究STAT5在脑缺血后的信号转导及其调控机制以及电针的干预作用,对了解电针治疗对脑缺血的内在干预机制有着一定的意义。实验方法同实验二。结果显示:与假手术组相比,造模后2小时组各指标明显升高,数值最高,24小时后数值降低,3天后进一步降低,接近假手术水平。其中模型2小时组在病灶侧皮质区和海马CA1区STAT5免疫阳性细胞个数两个指标与假手术2小时有显著性差异(P<0.05)。电针组数值变化趋势与模型组有一定的相似,即2小时组各指标明显升高,24小时后部分数值开始降低,但有部分指标反而有所升高,3天后所有指标均降低,但下降幅度明显低于模型组。与模型组相比,电针组各数据相均高于相应的模型组指标。其中,电针2小时组与模型2小时组相比,除病灶侧皮质区STAT5免疫阳性细胞平均光密度值外,其他病灶侧皮质区和海马CA1区的指标,在统计学上均有显著性差异(显著性分别为P<0.05到P<0.01)。电针3天组与模型3天组相比,除病灶侧皮质区STAT5免疫阳性细胞平均个数外,其他5个指标都与模型3天组均有显著性差异,显著性均为P<0.05。结果提示:电针在脑缺血超早期就能明显提高STAT5水平,激发机体的自我保护机制,同时,此种保护机制在电针干预下可以延续到3天后。提示,上调STAT5水平、激发由STAT5介导的自我保护机制可能是电针治疗脑缺血损伤的内在机制之一。3结论:综上所述:电针可以提高脑缺血模型大鼠学习记忆水平,其对缺血性脑损伤的功能改善内在机制可能与电针对脑缺血病灶区STAT系统调控作用有一定的关系,即抑制STAT1的水平和mRNA表达,提高STAT3、STAT5水平和STAT3mRNA的表达。通过此途径所形成的自身保护、修复机制的启动,达到抑制病灶区半暗带细胞的凋亡,恢复受损的脑组织的细胞功能。初步验证了“针刺刺激--信号调节-自稳态调节启动是其脑缺血局部自我修复的关键作用机制之一”的科学假说,为针灸治疗缺血性脑血管疾病提供了一定的科学依据和理论指导。

【Abstract】 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.

【关键词】 电针脑缺血STAT
【Key words】 ElectroacupunctureCerebral-IschemiaSTAT
  • 【分类号】R246
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