脑缺血后脑内STAT系统调控及电针干预作用的研究
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。
1.Background
Cerebrovascular 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 Study
2.1 Electroacupuncture on focal cerebral ischemia model of learning and memory in rats
In 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 STAT1mRNA
Caused 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 STAT3mRNA
STAT3 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 impact
Study 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.
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。
1.Background
Cerebrovascular 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 Study
2.1 Electroacupuncture on focal cerebral ischemia model of learning and memory in rats
In 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 STAT1mRNA
Caused 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 STAT3mRNA
STAT3 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 impact
Study 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.
引文
[1]Tarada K,Inao S,Mizutani N,et al.Cerebral blood flow,glucose metabolism and tunnel-positive cells in the development of ischemia[J].Cerebrovasc Dis,2001;11(1):9-18.
[2]Nitatori T,Sato N,Waguri S,et al.Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis[J].Neurosci,1995,15(2):1001-1011.
[3]Wiessner C,Sauer D,Alaimo D,et al.Protective effect of a caspase inhibitor in models for cerebral ischemia in vitro and in vivo[J].Cell Mol Biol(Noisy-le-grand),2000,46(1):53-62.
[4]朱晓东.凋亡通路及其研究进展[J].国外医学.生理、病理科学与临床分册,2002,(6):248-251.
[5]Planas AM,Gorina R,Chamorro A.Signalling pathways mediating inflammatory responses in brain ischaemia.Biochem Soc Trans.2006 Dec;34(Pt 6):1267-70],
[6]Zhang F,Wang S,Cao G,et al.Signal transducers and activators of transcription 5 contributes to erythropoietin-mediated neuroprotection against hippocampal neuronal death after transient global cerebral ischemia.Neurobiol Dis.2007;25(1):45-53.
[7]唐伟,孙忠人,王卓尔,白鹰针刺预处理对大鼠脑缺血再灌注损伤的保护作用 中国中医药科技2006:13(4):209-210
[8]陈泽斌,袁芳,梁凤霞,王华 针刺预处理脑组织提取液抗大鼠脑缺血再灌注损伤作用探讨中国针灸2004:24(5):347-350
[9]易玮,许能贵等 电针对局灶性脑缺血大鼠突触可塑性促进作用的实验研究中国中西医结合杂志2006,8(26):710-714
[10]汪帼斌,许能贵等 电针对局灶性脑缺血大鼠缺血区突触结构的影响中国临床康复2005:5(9):115-117
[11]徐振华,许能贵,易玮等 脑缺血大鼠缺血同侧海马齿状回突触可塑性的变化 中国临床康复2006:10(19):37-40
[12]徐振华,许能贵,符文彬等 不同刺激量针刺对脑缺血后功能恢复影响的临床研究江苏中医药2006:27(8):38-40
[13]易玮,许能贵,汪帼斌等 电针对局灶性脑缺血大鼠突触可塑性促进作用的 实验研究 中国中西医结合杂志2006;26(8):710-714
[14]徐振华,许能贵,易玮等 针刺对大鼠脑缺血后海马突触可塑性的促进作用安徽中医学院学报2007;26(3):18-23
[15]杜亦旭,许能贵,易玮等 电针对不同时间段局灶性脑缺血大鼠缺血区突触界面参数的影响 新中医2008;(1):93-95
[16]杜亦旭,许能贵,易玮等 电针对不同时间段局灶性脑缺血大鼠缺血区突触数密度、面密度的影响 广州中医药大学学报2008;25(3):224-228
[17]顾红卫;马维平;陈文;李启珊;刘兴勤;刘世红;喻强;刘惠玲;戴美堂针刺足三里和悬钟治疗缺血性脑卒中中国组织工程研究与临床康复 2007;11(25):4931-4933
[18]刘卫平;林展增;谭海彦;蔡昌龙;邢之华早期针灸治疗对缺血性脑卒中偏瘫患者运动功能恢复的影响河北北方学院学报·医学版2005.04.28;22(2):37-38
[19]饶萍;周莉;茅敏;白杨;温天明;唐宇红;郭文莉针刺治疗急性缺血性脑卒中随机对照观察中国针灸2006;26(10):694-696
[20]柳华;王毅;任惠;王文敏;马素萍针刺对缺血性脑卒中患者ADL能力和认知功能的影响中国康复医学杂志2006;21(5):444-448
[21]何扬子;王丽娜;黄力;王秀河;刘斯润;付跃高;韩冰;李静铭;胡静 针刺对缺血性中风患者食指运动激活脑功能区的影响中国针灸2006;26(5):357-361
[22]张慧萍;张丽;录海彬 针刺治疗急性缺血性脑卒中临床研究 实用诊断与治疗杂志 2005.02.10;19(2):144-145
[23]夏阳;朱天忠;宋亚光;杨林;冯祯钰;吉亚军;陈伟卫;袁慧;高俊雄(指导);高蔚头针结合CT影像定位治疗缺血性中风80例临床观察 上海针灸杂志2004.10.25;23(10):10-12
[24]韩为;杨骏(指导老师)益气活血化痰针刺方对中风患者细胞间黏附分子-1及生活质量的影响中医药临床杂志2006;18(2):141-142
[25]崔海;付于;王宝华;李沛手十二井穴放血法治疗缺血性中风急性期的临床观察中华实用中西医杂志2005.01.05;18(1):15-16
[26]丁兆琳;高利;谷世喆 针药结合治疗急性期缺血性脑卒中失语症的临床研究 中国中医药信息杂志2007;14(5):12-14
[27]王世广针刺督脉十三针治疗缺血性中风后哈欠频繁症98例 北京中医2006;25(3):173
[28]丁德光(1);孙国杰(2);李家康(1);罗惠平(1)针刺加灸治疗缺血性中风后假性球麻痹的临床研究中医药学刊2006;24(5):948-949
[29]肖晓华;李瑞春;朱红霞;帅记焱;徐明芳;傅缨(指导) 头穴透刺电针治疗缺血性中风临床观察上海针灸杂志2008;27(6):6-8
[30]王恩龙头针治疗缺血性中风临床研究针灸临床杂志 2006;22(9):30
[31]牛文民;李忠仁;黄国琪(Translator)Clinical Observation on Ischemic Apoplexy Treated by Scalp Multiple Needle Insertion with Electric Stimulation针灸推拿医学·英文版2006;4(4):219-222
[32]曾燕芬头体针治疗缺血性中风临床疗效观察辽宁中医杂志 2006;33(8):1020-1021
[33]雷正权;袁有才;许文骏 磁极针对极针刺治疗缺血性中风急性期的临床研究陕西中医学院学报2006;29(4):14-15
[34]牛文民;李忠仁头皮多点进针电刺激治疗缺血性脑中风临床观察上海针灸杂志2006;25(3):4-6
[35]韩舰华头皮针对急性缺血中风TCD的影响针灸临床杂志2004.08.20;20(8):21-22
[36]韩舰华头皮针治疗急性缺血性中风120例疗效观察上海针灸杂志2004.08.25;23(8):14-15
[37]李汶阳;刘智艳不同取穴方法治疗缺血性中风临床观察 上海针灸杂志2008;27(6):9-10
[38]张彦通;张中华;张勤婷;常通海头体针电交替治疗缺血性脑卒中疗效观察中国民康医学2008;20(1B):109
[39]李斌;张红星;李家康 补肾活血针刺法治疗缺血性中风的临床研究湖北中医杂志 2007;29(6):20-21
[40]徐振华;许能贵;符文彬;靳瑞(指导)不同刺激量针刺对脑缺血后功能恢复影响的临床研究江苏中医药2006;27(8):38-40
[41]庞勇;李雁;邹卓成;林军;何列涛;刘运珠益肾调督针法治疗缺血性中风30例临床观察江苏中医药2006;27(3):41-42
[42]林滨;俞征宙;陈岚榕;林宇凡;李中元针刺结合姿势控制训练对缺血性脑卒中患者康复疗效的影响中国康复医学杂志 2006;21(2):172-173
[43]苏红梅;吴远华;欧阳泠星;吴帮启;朱广旗 针刺督脉穴为主治疗缺血性脑血管病陕西中医学院学报 2005.05.25;28(3):42-44
[44]李斌;李家康(指导)针刺补肾活血法治疗缺血性中风的疗效观察中医药学刊2004.11.18;22(11):2106-2107
[45]林国华;李丽霞;李艳慧;张汉梁头体针结合治疗缺血性中风失语症的临床观察针灸临床杂志2005.08.20;21(8):25-26
[46]许新霞;焦伟;朱超英电头针治疗缺血性中风60例陕西中医2004.10.05;25(10):921-922
[47]李梅;袁军;王艳君氧针疗法治疗缺血性脑血管病例临床观察中华实用中西 医杂志 2004.09.05;17(17):2548-2549
[48]谭吉林;李国辉体针与头针治疗缺血性中风的对照研究中国针灸2004.06.12;24(6):371-373
[49]陈晓军;吴凌云;张家维(指导)温针灸治疗缺血性中风56例疗效观察针灸临床杂志2005.05.20;21(5):55-56
[50]王麟鹏;刘慧林;刘志顺;赵吉平;赵因;王桂玲;张晓霞;贺普仁(指导)贺氏三通法对缺血性中风患者神经功能缺损的影响:多中心随机对照研究 中国针灸2006;26(5):309-312
[51]何扬子;韩冰;胡静;原理;陈卓铭;李静铭;彭菊秀;王丽娜不同留针时间对针刺治疗缺血性中风疗效的影响新中医2005.01.05;37(1):58-60
[52]张玉杰急性缺血性脑卒中择时治疗32例临床研究中医杂志 2004.11.17;45(11):826-828
[53]刘悦;凌方明;蔡高宁;林雪霞;龙目恒头部电针治疗缺血性中风的效应差异中国针灸 2004.08.12;24(8):562-564
[54]杨秋汇头针治疗急性期缺血性中风194例血液流变学观察山西中医2007;23(4):54-56
[55]牛文民;李忠仁CT定位电头针治疗缺血性中风机理研究上海针灸杂志2006;25(7):3-4
[56]李雅洁;张红星;张唐法头针对缺血性脑卒中复发相关因素同型半胱氨酸、纤维蛋白原及抗凝血酶原Ⅲ含量的影响中国临床康复2006;10(23):1-3
[57]季杰;刘慧林;程金莲;王麟鹏三通法针刺对急性缺血性脑血管病患者血清TNF-α及IL-1β的影响中国中西医结合杂志2006;26(6):500-503
[58]陈文;谭敏;梁立安;翁泰来 艾灸足三里、悬钟对缺血性中风脑血管功能的影响及其临床意义中国针灸2006;26(3):161-165
[59]沈卫东;孔敏;张瑞雪 针药结合治疗对缺血性中风患者SOD、MDA影响的临床研究 河南中医学院学报2005.11.20;20(6):36-37
[60]王伟志;王占奎;赵建国;傅立新 针灸对缺血性脑血管病颈动脉粥样硬化患者血脂、血流变、LPO和SOD、ET和CGRP的影响 上海针灸杂志2005.07.25;24(7):19-23
[61]冯淑兰;杨路;古继红;李月梅;赖新生 颓三针与补阳还五汤合用对缺血性脑卒中患者白细胞介素-1β和白细胞介素6的影响 中国康复医学杂志2005.06.26;20(6):453-454
[62]李艳慧;李旅萍;林国华 病灶定位围针治疗缺血性中风的临床观察 广州中医药大学学报2004.09.15;21(5):376-378
[63]齐宇;何春慧;周丹;张福鼎;张彩荣 针灸治疗超早期缺血性中风16例近 期疗效观察 中国冶金工业医学杂志2004.06.15;21(3):191-192
[64]黄文权;唐绪刚;姜利鲲;邓明慧;曹文新 中药、针灸治疗脑卒中后遗症研究进展 中国中医急症 2008;17(1):88-89
[65]孔立红;孙国杰(指导)脑缺血耐受机制及针刺对脑缺血耐受机制可调性展望上海针灸杂志 2005.04.25;24(4):42-46
[66]丁炯;顾振;吴文忠;韩群颖;王鹤鸣;周建平;肖明;马瑞 电针预处理对大鼠局灶性脑缺血的影响 中国临床康复2004.01.05;8(1):106-107
[67]刘喆;赖新生 电针对局灶性脑缺血大鼠神经功能缺损及病理形态的影响中国针灸2005,25(12):879-884
[68.丁春华;刘焕荣;张少丹;凌亦凌 针灸治疗幼鼠缺血缺氧性脑病的实验研究 中国应用生理学杂志2005.11.28;21(4):400-401
[69]卜彦青:杜广中 头体针对脑缺血大鼠脑循环时效关系的实验研究 中医药学报 2004.04.20;32(2):26-27
[70]关玲;石现;杜元灏针刺对脑梗死大鼠脑微循环灌注状态的定性和定量分析中国临床康复 2005.08.07;9(29):238-240
[71]王少军;张立德(指导) 电针刺改善短暂性大脑中动脉梗塞大鼠中枢机能的实验研究 辽宁中医杂志2003.09.18;30(9):750-751
[72]张秀花;孙世晓;徐博佳 井穴点刺出血对局灶性脑缺血大鼠脑梗塞体积影响的基础研究 针灸临床杂志 2004.12.20;20(12):47-48
[73]丁春华;刘焕荣;张少丹;凌亦凌 针灸治疗幼鼠缺血缺氧性脑病的实验研究 中国应用生理学杂志2005.11.28;21(4):400-401
[74]黄碧兰;余良主;刘寿仙;王帮华 “手十二井穴”刺络放血对大鼠局灶性脑缺血后SOD活性和MDA含量的影响 咸宁学院学报·医学版 2005.02.15;19(1):4-6
[75]任玉录;孙德俊 电针对局灶性脑缺血急性期大鼠脑组织中自由基水平影响和神经功能相关性的实验研究 中西医结合心脑血管病杂志2008;6(6):679-681
[76]华金双;李丽萍;朱现民 艾灸预处理对全脑缺血大鼠SOD、MOA的影响 中国针灸 2006;26(8):595-597
[77]李刃;李忠仁;沈梅红;牛文民;林旭明 电针对脑缺血大鼠血清GSH、GSH-Px影响的研究 上海针灸杂志 2006;25(9):40-41
[78]姚凯;郭义;胡利民;曲竹秋 针刺对大鼠脑缺血超早期脑细胞内外游离钙离子浓度的影响 中国中西医结合急救杂志2005.09.28;12(5):303-305
[79]马惠芳;郭长青;邬继红;任秀君;严洁;林磊;金智秀;张露芬;图娅 针刺“水沟”穴与针药结合对实验性全脑缺血大鼠脑组织钙调素活性影响的实验研究 北京中医药大学学报 2003.01.30;26(1):84-85
[80]施昱丞;任秀君;洪银珠;图娅 电针对高血脂合并脑缺血大鼠治疗前后血脂含量变化的影响 中国康复医学杂志2007:22(3):225-229
[81]王述菊;孙国杰;吴绪平;黄伟;丁昀 电针百会、水沟对急性脑梗死大鼠凝血和纤溶系统影响的研究 世界针灸杂志·英文版 2008;18(2):23-27
[82]孙忠人;佘军;吴燕|JING|针刺对急性局灶性脑缺血大鼠血清白蛋白、球蛋白含量及其比率的影响 中国中医药科技2004.09.20;11(5):261-262
[83]杨静;熊利泽:王强;刘艳红 阿片受体在电针预处理诱导大鼠脑缺血耐受效应中的作用 中华老年多器官疾病杂志 2006:5(3):218-221
[84]余晓慧,孙国杰 针刺对局灶性脑缺血大鼠脑细胞凋亡及Bcl-2蛋白表达的影响J.针刺研究,2004,1(29):15-17
[85]卜渊,耿德勤,曾因明.针刺调节脑缺血再灌后细胞凋亡相关基因表达的研究进展J.针刺研究,2003,4(28):288-291
[86]张春红,王舒,郑灏泳,等 针刺对局灶性脑缺血大鼠脑细胞凋亡的影响J.针刺研究,2003,2(26):102-105
[87]高明灿,王淑斌.针刺对缺血缺氧性脑性瘫痪幼鼠脑细胞凋亡及含水量的干预效应J.中医康复研究,2005,9(21):132-133
[88]田代实,邓医宇,王光海,等 针刺预处理对大鼠局灶性脑缺血的抗细胞凋亡作用 J.第四军医大学学报,2004,25(1):27-29
[89]倪金霞;高维滨;朱文增;姜建玲;吴壮项针疗法对急性脑梗死大鼠病理学及bel-2表达的影响 针灸临床杂志2007:23(6):46-47
[90]孙忠人;张力;唐伟;李晓捷;单丽莉:马睿杰 针刺预处理对全脑缺血大鼠脑组织细胞凋亡的影响 中国临床康复2006;10(15):144-145
[91]王秀云;李积胜;郭义;刘公望:潘荣菁;李桂兰;韩煜;王强;张果忠手十二井穴刺络放血法对MCAO模型大鼠大脑皮层c-fos蛋白表达的影响上海针灸杂志2004.23(12):39-41
[92]余晓慧 电针对局灶性缺血大鼠Fas蛋白表达的影响 江西中医学院学报2005.02.15;17.(1):40
[93]余晓慧 电针对局灶性脑缺血大鼠bax蛋白表达的影响 河南中医2005.02.10;25(2):30
[94]余晓慧电针对局灶性脑缺血大鼠c-fos蛋白表达的影响甘肃中医2005.05.15;18(5):41-42
[95]余晓慧 电针对局灶性脑缺血大鼠Caspase-3蛋白表达的影响 辽宁中医学院学报2005.03.18;7(2):167
[96]冉群芳;倪光夏 针刺对脑缺血后细胞凋亡相关基因表达影响的研究进展上海针灸杂志 2007;26(7):46-48
[97]韩冰冰;宋文丽;宋炳玉;王世军 针刺对脑缺血模型动物凋亡相关基因表达影响的研究进展现代中医药 2005.01.25;(1):58-60
[98]霍国敏;周爽;薛茜;石武年 十二井穴刺络放血对局灶性脑缺血模型大鼠神经细胞功能的影响山东中医杂志 2006;25(7):477-478
99]李家康;何伟;刘又香;陈墩寿;张茂林 电针对局灶性脑缺血大鼠脑组织TNF-α和NO含量的影响 中医药学刊2004.02.18;22(2):203-204
[100]洪银珠;任秀君;施昱丞;韩止荣;金智秀;图娅 电针干预对高血脂合并脑缺血大鼠血脂四项及TNF-α含量的影响 针灸临床杂志 2007;23(4):51-55
[101]马惠芳;图娅;马文珠;郭长青;郝晋东:邬继红 “十二井穴”针法对局灶性脑缺血大鼠脑皮质及血清肿瘤坏死因子-α含量的影响 针刺研究 2006;31(1):35-37,42
[102]李忠仁;崔龙;沈梅红;项晓人 电针对脑纹状体缺血性神经元细胞凋亡及基因表达的调整中国临床康复 2006;10(7):105-107
[103]唐伟;王威:孙忠人;张力 针刺预处理全脑缺血大鼠海马CA1区Bcl-2mRNA的表达 中国中医基础医学杂志 2007;13(2):156-158
[104.唐伟;孙忠人;张力;王威 针刺预处理全脑缺血大鼠海马CA1区细胞凋亡和热休克蛋白70mRNA的表达 中国临床康复2005.10.07;9(37):90-92
[105]余晓慧 电针对局灶性脑缺血大鼠热休克蛋白70表达的影响现代 中西医结合杂志 2005.07.20;14(14):1831
[106]王秀云;李积胜;刘公望;郭义;张果忠;潘荣菁;王强;李桂兰;韩煜 井穴刺络放血法对MCAO模型大鼠大脑皮层HSP70蛋白表达的影响 天津中医药2005.22(6):477-479
[107]黄碧兰;程静 “手十二井穴”刺络放血对大鼠局灶性脑缺血后N0含量和NOS活性的影响 咸宁学院学报·医学版2004.10.15;18(5):312-314
[108]黄碧兰;余良主;程静 “手十二井穴”刺络放血对大鼠局灶性脑缺血后一氧化氮合酶活性的干预作用 中国临床康复2006;10(7):174-176
[109]高锋;何伟;陈墩寿;李家康 电针“人中”、“内关”对急性脑缺血大鼠血清一氧化氮的影响 中华现代临床医学杂志2004.01.15;2(1):4-5
[110]郭永明;梁宪如;杜元灏;郭永铁;石学敏 醒脑开窍针法对局灶性脑缺血大鼠脑组织及血清IL-1β含量的影响 上海针灸杂志 2004.08.25;23(8):35-37
[111]曲金柱;李宛青 电针刺激百会及大椎穴对新生鼠缺氧缺血性脑损伤的保护 中国临床康复2005.08.07;9(29):249-251
[112]陈永胜;陈凤琴;赵建新:田元祥 电针对血管性痴呆小鼠脑组织超氧 化物岐化酶、丙二醛及乙酰胆碱酯酶的影响 中国临床康复2005.03.07;9(9):111-113
[113]王世军;崔可密;卢岩;郭继龙;韩冰 针刺对MCAO大鼠海马CA3区微血管数目及神经元死亡率的影响山东中医药大学学报 2005.01.15;29(1):59-60
[114]杨文清;王琦;王俊卿;郭克锋针刺改善慢性全脑缺血缺氧性大鼠认知功能的机理 中国康复2007;22(4):225-227
[115]卢雨微;吕明庄;贺志光耳穴埋针对血管性痴呆大鼠记忆障碍及B淀粉样蛋白表达的影响 中国针灸2006;26(11):804-808
[116]赵宇辉;孙忠人;李晓捷;李蕾 艾灸预处理对全脑缺血大鼠海马CA1区Bcl-2和Bax蛋白表达影响的实验研究 针灸临床杂志2006;22(8):53-54
[117]张慧敏;费宇彤;时宇静;贾宝辉;图娅(指导) 针刺“百会”“太阳”改善局灶性脑缺血脑微血管内皮细胞功能的动态观察 针刺研究2006;31(2):67-72,封3
[118]唐伟;孙忠人;张力;王威:王卓尔;白鹰 针刺预处理全脑缺血大鼠海马CA1区B细胞淋巴瘤2mRNA的表达中国临床康复2006:10(11):123-125
[119]陈振虎:赖新生;江钢辉 电针四神聪穴对实验性血管性痴呆大鼠中枢胆碱能神经元的影响 现代中西医结合杂志2006;15(14):1884-1885
[120]赵慧英;牟萍;董岩 病理条件下的神经可塑性及在针灸研究中的可能应用 针刺研究2008,33(1):41-46
[121]Williams JM,Guevremont D.Kennard JT.et al.Long-term regulation of N-methyl-D-aspartate receptor subunits and associated synaptic proteins following hippocampal synaptic plasticity.Neuroscience.2003.118:1003-1013.
[122]Chetkovich DM,chen L,Stocker TJ,et al.Phosphorylation of the postsynaptic density-95(PSD-95) / discs large / zona occludens-1 binding site of stargazin regulates binding to PSD-95 and synaptic targeting of AMPA receptors.J Neurosci.2002.22:5791-5796.
[123]Schnell E,Sizemore M,Karimzadegan S.et al.Direct interactioas between PSD-95 and stargazin control synaptic AMPA receptor number.Proc Natl Acad Sci USA,2002,99:13902-13907.
[124]Kalia Lv.Salter MW.Interactioas between Src family protein tyrosine kinases and PSD-95.Neuropharmacology.2003.45:720-728.
[125]杜亦旭;许能贵;易玮;黄国新;蔡通;黄真炎;吴玲霓 电针对不同时间段局灶性脑缺血大鼠缺血区突触数密度、面密度的影响 广州中医药大学学报 2008;25(3):224-228
[126]白晶;李宝栋;唐强(指导);邢殿文 头穴丛刺法对急性缺血性脑梗死大鼠神经可塑性影响的实验研究 针灸临床杂志2005.06.15;21(6):47-48
[127]汪帼斌;许能贵;佘世锋;易玮;黄真炎;赖新生 电针对局灶性脑缺血大鼠缺血区突触结构的影响 中国临床康复2005.02.05;9(5):115-117
[128]杨卓欣;于海波;王玲;皮敏;张家维 电针对缺血性脑损伤大鼠海马齿状回突触传递活动的影响 广州中医药大学学报2005.03.15;22(2):118-122
[129]易玮;许能贵;汪帼斌;佘世锋;徐振华;赖新生 电针对局灶性脑缺血大鼠缺血区皮层神经生长因子表达的影响 广州中医药大学学报 2006:23(1):35-38
[130]范郁山;罗燕 浅刺针法对脑梗塞大鼠的脑组织缺血半暗带NGF表达的影响针灸临床杂志2008;24(1):36-38
[131]纪中 电针百会穴对大鼠缺血区脑组织神经生长因子影响的研究 浙江中医学院学报 2005.05.15;29(3):67
[132]许能贵;汪帼斌;佘世锋;易玮;赖新生针刺百会、大椎穴对局灶性脑缺血大鼠皮层脑源性神经营养因子表达的影响 广州中医药大学学报 2004.11.15;21(6):439-442
[133]胡圣望;胡勇;胡亚林:吴红年 新生大鼠脑缺血缺氧后脑组织脑源性神经营养因子表达及电针的干预效应 中国临床康复2006;10(35):84-86
[134]蒋红芝:黄光英;张明敏 针刺对局部脑缺血大鼠血管内皮生长因子表达和脑血流的影响 微循环学杂志2006;16(2):9-11,封2
[135]李宝栋;王志勇;白晶;白海娟;公维志;闫瑞萍;刘振江;王利春 头穴丛刺对大鼠缺血脑组织血管内皮生长因子表达的影响 世界针灸杂志·英文版2008:18(1):38-44
[136]李红颖;朱文增;东贵荣;王凤军:客蕊 头穴透刺对急性脑梗死大鼠神经丝蛋白-200的影响上海针灸杂志 2007;26(8):40-42
[137]李红颖;朱文增;东责荣;王凤军;客蕊;崔学军(翻译) Influence of Scalp Point-through-point Acupuncture on 200 kDa Neurofilament Protein in Rats with Acute Cerebral Infarction 针灸推拿医学·英文版 2007;5(6):341-344
[138]钱长晖;毛庆菊;王芳;吴艳;刘冠男;罗涛 电针对大鼠脑缺血海马损伤区神经元δ-连环素表达的影响 福建医药杂志2007;29(2):82-84
[139]杨卓欣;于海波;饶晓丹:刘远声;皮敏 任脉电针对脑缺血大鼠侧脑室下区神经干细胞增殖与分化的影响 中医杂志 2006;47(6):429-432
[140]张慧敏 头穴针刺对局灶性脑缺血大鼠脑微血管内皮第八因子相关抗原影 响的动态观察 中国康复医学杂志2006;21(4):289-292
[141]李铁浪;严洁;邓常青;沈菁;胡蓉;王灵 电针不同穴组对急性脑缺血大鼠脑组织NPY及其基因表达的影响 湖南中医学院学报2006:26(2):43-45
[142]胡俊;李玲;张海鸥;吴军 脑缺血后可逆性蛋白磷酸化水平变化及电刺激对其的影响 中西医结合心脑血管病杂志2006;4(7):603-606
[143]耿战辉,程义勇 重新认识神经胶质细胞 生理科学进展.2003,34(3):231-234
[144.陈明明;成泽东;陈以国(指导) 论小胶质细胞在针灸治疗缺血性脑病研究中的新思路 中医药学刊2005.09.15;23(9):1629-1630
[145]罗燕,许能贵,易玮,杜亦旭.电针对局灶性脑缺血大鼠缺血灶周围区星形胶质细胞谷氨酸转运体的影响.安徽中医学院学报.2009,28(1):30-33
[146]谭峰:万赛英;王海侨 电针对轴突生长与抑制因子的干预 中国临床康复2006;10(23):152-154
[147]刁利红;杨卓欣;罗文舒电针任脉联合bFGF对脑缺血大鼠ERK通路的调节作用 中医药信息2006;23(3):17-20
[148]呙登俊;赵永波;陈英辉 针刺对缺血性脑损伤大鼠的治疗作用及对GDNF 表达水平和MAPKs信号转导通路的调节 神经科学通报·英文版 2005.11.30;21(6):385-390
[149]陈泽斌;王华 针刺对大鼠脑组织神经生物学基因表达的研究 中国针灸2005.08.12;25(8):573-576
[150.曾俊:严洁(指导) 针灸对急性期脑缺血保护作用机制研究进展 中医药导报2008:14(1):72-75
[151]Robert F Thamas M.Rapid ischemic cell death in immature oligodendrocytes:a fetal glutamate release feed back loop[J].Neuroscience,2000,20(1):34-42.
[152]Nitatori T,Sato N,Waguri S,et al.Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis[J].Neurosci,1995,15(2):1001-1011.
[153]Sun JJ,Liu Y,et al.Effects of P2Y1 receptor on glial fibrillary acidic protein and glial cell line-derived neurotrophic factor production of astrocytes under ischemic condition and the related signaling pathways.Neurosci Bull.2008;24(4):231-43.
[154]Shyu WC,Lin SZ,et al.Secretoneurin promotes neuroprotection and neuronal plasticity via the Jak2/Stat3 pathway in murine models of stroke.J Clin Invest.2008;118(1):133-48.
[155]Ihle JN.STATs:Signal transducers and activators of transcription [J],Cell,1996,84(3):331-334.
[156]Pellegrini S,Dusanterfourt I.The structure,regulation an d function of the Janus kinases(JAKs)and the signal transducers and activators of transcription(STATs)[J].Eur J Biochem,1997,248(3):615-633.
[157]Kisseleva T,Bhattacharya S,Braunstein J,et al.Signaling through the JAK-STAT pathway:recent advances and future challenges[J].Gene,2002,285(1):1-24.
[158]Planas AM,Soriano MA,et al.Induction of Stat3,a signal transducer and transcription factor,in reactive microglia following transient focal cerebral ischaemia.Eur J Neursci,1996,8(12):2612-2618.
[159]李文涛等 慢性脑缺血对信号转导和转录激活因子-1的表达 中国实用神经疾病杂志2007:10(3):82-83
[160]李洪春:马萍等 脑缺血/再灌注诱导大鼠信号转导与转录激活子-1的变化 中华医学研究杂志2006:6(5):484-486
[161]Takagi Y,Harada J,Chiarugi A,et al.STATI is activated in neurons after ischemia and contributes to ischemic brain injury[J].J Cereb Blood FlowMetab,2002,22(I1):1311-1318.
[162]Justicia C.Gabriel C,et al.Activat ion of the JAKS/STATS pathway following transient focal cerebral ischemia:signaling thigh Jakl and STAT3in astrocytes.Glia,2000,30:253-270.
[163]Wen TC,Peng H,Hata R,et al.Induction of phosphorylated-STAT3following focal cerebral ischemia in mice.Neurosci Lett,2001,303(3):153-56.
[164]谢惠芳 刘振华 朱利元 大鼠脑缺血再灌注损伤后脑组织STAT3变化的免疫组织化学研究 临床神经病学杂志2000.12.25:13(6):329-331
[165]Satriotomo I,Bowen KK,Vemuganti R.JAK2 and STAT3 activation contributes to neuronal damage following transient focal cerebral ischemia.J Neurochem.2006;98(5):1353-68.
[166]Yamashita T,Sawamoto K,Suzuki S,et al.Blockade of interlrukin-6sign aling aggravates ischem ic cerebral damage in m ice:possibleinvolvement of STAT3 activation in the protection of neurons[J]JNeurochem,2005,94(2):459-468.
[167]Dziennis S,Alkayed NJ Role of signal transducer and activator of transcription 3 in neuronal survival and regeneration.Rev Neurosci.2008;19(4-5):341-61.)
[168]苟俊 潘峰等 低氧状态下海马神经元细胞信号转录因子和活化子3,5的基因表达状况 中国临床康复2004.01.05:8(1):66-67
[169]Chong ZZ,Kang JQ,Maiese K.Hematopoietic factor erythropoietin fosters neuroprotection through novel signal transduction cascades.J Cereb Blood Flow Metab.2002:22(5):503-14.
[170]苑晓玲 细胞因子信号转导负调控蛋白-SOCS家族研究进展 国外医学·内分泌学分册2001,21(2):83-85
[171]许能贵,易玮,马勤耘等.电针对大鼠局灶性脑缺血后神经元损伤保护作用的研究.中国针灸,2000;20(4):237-240。
[172]陈忠义;张发荣;李寅超 浅谈中医对血管性认知障碍的认识 辽宁中医药大学学报2007:9(2):33-34.
[173]韩济生主编.神经科学纲要.北京医科大学、中国协和医科大学联合出版社,1993.723-736..
[174]Yonemori F,Yamaguchi T,Yamada H,et al.Spatial cognitive performance after chronic focal ischemia in ratsJ..J Cereb Blood Flow Metab,1999,19(5):483-94.
[175]谢集建 缺氧缺血性脑损伤对学习记忆的影响及其机制研究进展 国外医学·妇幼保健分册2001,12(2):83-85.
[176]曹新生 孙喜庆 吴兴裕 实验性脑缺血性损伤与学习记忆功能 中华航空航天医学杂志2005,16(2):157-160.
[177]谢集建.缺氧缺血性脑损伤对学习记忆的影响及其机制研究进展.国外医学妇幼保健分册,2001,12(2):83--85.
[178]Wen TC,Matsuda S,Yoshimuro H,et al.Ciliary neurotropic factor prevents ischemia induced learning disability and neuronal loss in gerbilsJ.Neurosci Lett.1995,19:55-58.
[179]Araki T,Kato H,Kogure K.Selective neuronal vulnerability following transient cerebral ischemia in the gerbil:distribution and time course.Acta Neurol Scand,1989,80(6):548-553.
[180]Briones TL,Therrien B.Behavioral effects of transient cerebral ischemia.Bio Res Nurs,2000,1(4):276-286.
[181]谢集建,常燕群,陈宝芳,等.新生大鼠缺血低氧性脑损伤后学习记忆和海马神经元超微结构的研究.中华急诊医学杂志,2001,10(3):155-157.
[182]姚国恩,王景周,陈曼娥,等.血管性痴呆大鼠海马区长时程增强变化的研究.中国行为医学科学,2002,11(4):368-370.
[183]Rison R A,Stanton P K.Long-term potentiation and N- methyl-D-aspartate receptors:foundation of memory and neurologic diseaseJ.Neurosci-biobehav-rev.1995,19(4):533-552.
[184]Lyubkin M.Duzand DM,Haxhiu MA.Interaction between tetanus Long - term potentiation and hypoxia - induced potentiation in the rat hippocampusJ..Neurophysiol,1997,78(5)2475-2482.
[185]Hsu KS,Huang CC.Characterization of the anoxia-induced Long-terln synaptie potentiation in area CAlot the rat hippocampusD.British J of Pharmcol,1997,i22:671-681.
[186]沈维高,何欣,冯利民,等.老年大鼠在空间辨别性学习记忆时海马Ach 和Ach能纤维的变化J.中国老年学杂志,2006,26(11):1528-1529.
[187]Dunbar GL,Rylett RJ,Schnidt BM,et al.Hippocampal choline acetyltransferase activity correlates with spatial learning in aged ratsJl.Brain Res,1993,604:266-272.
[188]张军艳,张博爱,朱红灿,黄晓琳 学习记忆训练对全脑缺血大鼠认知能力的影响及其胆碱能机制 中国康复医学杂志,2008,23(4):305-308.
[189]Nagakura A,M iyake TK,Takagi N,et al.Impairment of adenylyl cyclase and of spatial memory function after microsphere embolism in rats.J Neurosci Res,2002,68(3):363-372.
[190]Nagakura A,Takagi N,Takeo S.Im pairment of cerebral cAMP-mediated signal transduction system and of spatial memory function after microsphere embolism in rats.Neuroscience,2002,I13(3):519-528.
[191]姚国恩,王景周,陈曼娥.血管性痴呆大鼠认知障碍的N-甲基D-天冬氨酸受体机制.中国临床康复,2003,7(10):1496-1498.
[192]张雪朝,吕明庄,贺志光,等针刺对VD大鼠记忆障碍及c-fos mRNA和蛋白表达的影响.中国康复医学杂志,2001,16(2):74-76.
[193]张雪朝,贺志光,吕明庄,等.血管性痴呆大鼠记忆障碍与海马Bcl-2蛋白表达的研究.中国病理生理杂志,2002,18(10):1294-1295.
[194]王黎,赖新生,雷娓娓电针对全脑缺血大鼠学习记忆能力和海马神经元超微结构的影响中国针灸2002,22(1):47-50.
[195]闫兵;许能贵;唐纯志;何利雷;绍瑛 电针对血管性痴呆大鼠学习记忆能力的改善作用及其机理探讨 广州中医药大学学报2007:24(3):215-218
[196]卢雨微;吕明庄;贺志光 耳穴埋针对血管性痴呆大鼠记忆障碍及β淀粉样前体蛋白表达的影响 上海针灸杂志 2007:26(5):44-46
[197]张玲 张为众 针刺对反复短暂脑缺血再灌注大鼠脑损伤的影响 中国老年学杂志2007,12(2.:2387-2389.
[198]许能贵:易玮:马勤耘:许冠荪:朱舜丽:陈全珠 电针对大鼠局灶性脑缺血后神经元损伤保护作用的研究 中国针灸2000.04.12:20(4):237-240
[199]许能贵:易玮;赖新生;靳瑞电针对局灶性脑缺血大鼠脑细胞内Ca2+含量的影响 中国中西医结合杂志2002.04.20;22(4):295-297
[200]骆仲达;骆仲逵;许能贵;赖新生电针对局灶性脑缺血大鼠脑源性神经营养因子影响的研究 针刺研究2002.06.15:27(2):105-107
[201]骆仲达:赖新生(指导):许能贵 电针督脉对缺血性脑损伤大鼠神经细胞凋亡的影响 安徽中医学院学报2002.12.01;21(6):27-29
[202]骆仲达;骆仲逵;许能贵;赖新生电针对局灶性脑缺血大鼠缺血区脑组织神经细胞凋亡及神经生长因子影响的研究 针刺研究2002.09.15;27(3):165-169
[203]汪帼斌;许能贵;佘世锋;易玮;黄真炎;赖新生 电针对局灶性脑缺血大鼠缺血区突触结构的影响 中国临床康复2005.02.05:9(5):115-117
[204]徐振华(1);许能贵(2);易玮(2);靳瑞(2)脑缺血大鼠缺血同侧海马齿状回突触可塑性的变化中国临床康复2006;10(19):37-40
[205]徐振华;许能贵;易玮;靳瑞 脑缺血大鼠缺血同侧海马齿状回突触可塑性的变化 中国临床康复2006;10(19):37-40
[206]徐振华;许能贵;易玮;符文彬;靳瑞 针刺对大鼠脑缺血后海马突触可塑性的促进作用 安徽中医学院学报2007;26(3):18-23
[207]易玮;许能贵;汪帼斌;徐振华;余世锋;黄真炎;赖新生 电针对局灶性脑缺血大鼠突触可塑性促进作用的实验研究 中国中西医结合杂志2006:26(8):710-714
[208]杜亦旭;许能贵;易玮;黄国新;蔡通;黄真炎;吴玲霓 电针对不同时间段局灶性脑缺血大鼠缺血区突触数密度、面密度的影响 广州中医药大学学报2008;25(3):224-228
[209.胡镜清,温泽淮,赖世隆等Morris术迷宫检测的记忆属性与方法学初探广州中医药大学学报2000,17(2):117-1 19.
[210]Block F.Global ischem ia and behavioural deficits.Prog Neurobiol,1999,58(3):279-295.
[211]尹军祥 田金洲 程龙 时晶 等MCAO模型大鼠学习记忆特征中国行为医学科学2006年3月第15卷第3期197-199.
[212]姚国恩,王景周,陈曼娥,等.血管性痴呆大鼠海马区长时程增强变化的研究 中国行为医学科学,2002,11(4):368-370.
[213]曹贵方 杨期东JAK-STAT信号转导途径与脑缺血 国外医学神经病学神经外科学分册2004,31(4):340-343.
[214]Wagner FD,Buz S,Knosalla C,et al.Modulation of circulating endothelin-1 and big-endothelin by nitric oxide inhalation following left ventricular assist device implantationJ..Circulation,2003,108(Suppl 1):278-284.
[215]Amana CV,Grammatikakis N,Chernov M,et al.Regulation of c-myc expression by IFN -through Statl dependent and independent pathwaysJ..EM BO J,2000,19(2):263-272
[216]谢惠芳 徐如祥 姜晓丹JAKs-STATs信号转导通路与缺血性脑损伤 中华神经医学杂志2006,5(10):1071-1072,1075
[217]曹贵方 杨期东JAK-STAT信号转导途径与脑缺血 国外医学神经病学神经外科学分册2004,31(4):340-343
[218]Suzuki S,Tanaka K,Nngawa S.et al.Phospharylatian of signal transducer and activators of transcription-3(stat3) after focal cerebral ischemia in rats.Exp Neurol.2001.170:63-71.
[219]Choi JS,Kim SY,Cha JH,et al.Upregulation of gp130 and STAT3activation in the rat hippocampus following transient forebrain ischemia.Glia,2003,41(3):237-246.
[220]Li H,Zhang Q,Zhang G.Signal transducer and activator of transcription-3 activation is mediated by N-methyl-D-aspartate receptor and L-type voltage-gated Ca~(2+)channel during cerebral ischemia in rat hippocampus.Neuronsci Lett,2003,345(1):61-64.
[221]Byts N,Samoylenko A,Fasshauer T,Ivanisevic M,Hennighausen L,Ehrenreich H,Siren AL.Essential role for Stats in the neurotrophic but not in the neuroprotective effect of erythropoietin.Cell Death Differ.2008Apr;15(4):783-92.Epub 2008 Feb 8.
[2]Nitatori T,Sato N,Waguri S,et al.Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis[J].Neurosci,1995,15(2):1001-1011.
[3]Wiessner C,Sauer D,Alaimo D,et al.Protective effect of a caspase inhibitor in models for cerebral ischemia in vitro and in vivo[J].Cell Mol Biol(Noisy-le-grand),2000,46(1):53-62.
[4]朱晓东.凋亡通路及其研究进展[J].国外医学.生理、病理科学与临床分册,2002,(6):248-251.
[5]Planas AM,Gorina R,Chamorro A.Signalling pathways mediating inflammatory responses in brain ischaemia.Biochem Soc Trans.2006 Dec;34(Pt 6):1267-70],
[6]Zhang F,Wang S,Cao G,et al.Signal transducers and activators of transcription 5 contributes to erythropoietin-mediated neuroprotection against hippocampal neuronal death after transient global cerebral ischemia.Neurobiol Dis.2007;25(1):45-53.
[7]唐伟,孙忠人,王卓尔,白鹰针刺预处理对大鼠脑缺血再灌注损伤的保护作用 中国中医药科技2006:13(4):209-210
[8]陈泽斌,袁芳,梁凤霞,王华 针刺预处理脑组织提取液抗大鼠脑缺血再灌注损伤作用探讨中国针灸2004:24(5):347-350
[9]易玮,许能贵等 电针对局灶性脑缺血大鼠突触可塑性促进作用的实验研究中国中西医结合杂志2006,8(26):710-714
[10]汪帼斌,许能贵等 电针对局灶性脑缺血大鼠缺血区突触结构的影响中国临床康复2005:5(9):115-117
[11]徐振华,许能贵,易玮等 脑缺血大鼠缺血同侧海马齿状回突触可塑性的变化 中国临床康复2006:10(19):37-40
[12]徐振华,许能贵,符文彬等 不同刺激量针刺对脑缺血后功能恢复影响的临床研究江苏中医药2006:27(8):38-40
[13]易玮,许能贵,汪帼斌等 电针对局灶性脑缺血大鼠突触可塑性促进作用的 实验研究 中国中西医结合杂志2006;26(8):710-714
[14]徐振华,许能贵,易玮等 针刺对大鼠脑缺血后海马突触可塑性的促进作用安徽中医学院学报2007;26(3):18-23
[15]杜亦旭,许能贵,易玮等 电针对不同时间段局灶性脑缺血大鼠缺血区突触界面参数的影响 新中医2008;(1):93-95
[16]杜亦旭,许能贵,易玮等 电针对不同时间段局灶性脑缺血大鼠缺血区突触数密度、面密度的影响 广州中医药大学学报2008;25(3):224-228
[17]顾红卫;马维平;陈文;李启珊;刘兴勤;刘世红;喻强;刘惠玲;戴美堂针刺足三里和悬钟治疗缺血性脑卒中中国组织工程研究与临床康复 2007;11(25):4931-4933
[18]刘卫平;林展增;谭海彦;蔡昌龙;邢之华早期针灸治疗对缺血性脑卒中偏瘫患者运动功能恢复的影响河北北方学院学报·医学版2005.04.28;22(2):37-38
[19]饶萍;周莉;茅敏;白杨;温天明;唐宇红;郭文莉针刺治疗急性缺血性脑卒中随机对照观察中国针灸2006;26(10):694-696
[20]柳华;王毅;任惠;王文敏;马素萍针刺对缺血性脑卒中患者ADL能力和认知功能的影响中国康复医学杂志2006;21(5):444-448
[21]何扬子;王丽娜;黄力;王秀河;刘斯润;付跃高;韩冰;李静铭;胡静 针刺对缺血性中风患者食指运动激活脑功能区的影响中国针灸2006;26(5):357-361
[22]张慧萍;张丽;录海彬 针刺治疗急性缺血性脑卒中临床研究 实用诊断与治疗杂志 2005.02.10;19(2):144-145
[23]夏阳;朱天忠;宋亚光;杨林;冯祯钰;吉亚军;陈伟卫;袁慧;高俊雄(指导);高蔚头针结合CT影像定位治疗缺血性中风80例临床观察 上海针灸杂志2004.10.25;23(10):10-12
[24]韩为;杨骏(指导老师)益气活血化痰针刺方对中风患者细胞间黏附分子-1及生活质量的影响中医药临床杂志2006;18(2):141-142
[25]崔海;付于;王宝华;李沛手十二井穴放血法治疗缺血性中风急性期的临床观察中华实用中西医杂志2005.01.05;18(1):15-16
[26]丁兆琳;高利;谷世喆 针药结合治疗急性期缺血性脑卒中失语症的临床研究 中国中医药信息杂志2007;14(5):12-14
[27]王世广针刺督脉十三针治疗缺血性中风后哈欠频繁症98例 北京中医2006;25(3):173
[28]丁德光(1);孙国杰(2);李家康(1);罗惠平(1)针刺加灸治疗缺血性中风后假性球麻痹的临床研究中医药学刊2006;24(5):948-949
[29]肖晓华;李瑞春;朱红霞;帅记焱;徐明芳;傅缨(指导) 头穴透刺电针治疗缺血性中风临床观察上海针灸杂志2008;27(6):6-8
[30]王恩龙头针治疗缺血性中风临床研究针灸临床杂志 2006;22(9):30
[31]牛文民;李忠仁;黄国琪(Translator)Clinical Observation on Ischemic Apoplexy Treated by Scalp Multiple Needle Insertion with Electric Stimulation针灸推拿医学·英文版2006;4(4):219-222
[32]曾燕芬头体针治疗缺血性中风临床疗效观察辽宁中医杂志 2006;33(8):1020-1021
[33]雷正权;袁有才;许文骏 磁极针对极针刺治疗缺血性中风急性期的临床研究陕西中医学院学报2006;29(4):14-15
[34]牛文民;李忠仁头皮多点进针电刺激治疗缺血性脑中风临床观察上海针灸杂志2006;25(3):4-6
[35]韩舰华头皮针对急性缺血中风TCD的影响针灸临床杂志2004.08.20;20(8):21-22
[36]韩舰华头皮针治疗急性缺血性中风120例疗效观察上海针灸杂志2004.08.25;23(8):14-15
[37]李汶阳;刘智艳不同取穴方法治疗缺血性中风临床观察 上海针灸杂志2008;27(6):9-10
[38]张彦通;张中华;张勤婷;常通海头体针电交替治疗缺血性脑卒中疗效观察中国民康医学2008;20(1B):109
[39]李斌;张红星;李家康 补肾活血针刺法治疗缺血性中风的临床研究湖北中医杂志 2007;29(6):20-21
[40]徐振华;许能贵;符文彬;靳瑞(指导)不同刺激量针刺对脑缺血后功能恢复影响的临床研究江苏中医药2006;27(8):38-40
[41]庞勇;李雁;邹卓成;林军;何列涛;刘运珠益肾调督针法治疗缺血性中风30例临床观察江苏中医药2006;27(3):41-42
[42]林滨;俞征宙;陈岚榕;林宇凡;李中元针刺结合姿势控制训练对缺血性脑卒中患者康复疗效的影响中国康复医学杂志 2006;21(2):172-173
[43]苏红梅;吴远华;欧阳泠星;吴帮启;朱广旗 针刺督脉穴为主治疗缺血性脑血管病陕西中医学院学报 2005.05.25;28(3):42-44
[44]李斌;李家康(指导)针刺补肾活血法治疗缺血性中风的疗效观察中医药学刊2004.11.18;22(11):2106-2107
[45]林国华;李丽霞;李艳慧;张汉梁头体针结合治疗缺血性中风失语症的临床观察针灸临床杂志2005.08.20;21(8):25-26
[46]许新霞;焦伟;朱超英电头针治疗缺血性中风60例陕西中医2004.10.05;25(10):921-922
[47]李梅;袁军;王艳君氧针疗法治疗缺血性脑血管病例临床观察中华实用中西 医杂志 2004.09.05;17(17):2548-2549
[48]谭吉林;李国辉体针与头针治疗缺血性中风的对照研究中国针灸2004.06.12;24(6):371-373
[49]陈晓军;吴凌云;张家维(指导)温针灸治疗缺血性中风56例疗效观察针灸临床杂志2005.05.20;21(5):55-56
[50]王麟鹏;刘慧林;刘志顺;赵吉平;赵因;王桂玲;张晓霞;贺普仁(指导)贺氏三通法对缺血性中风患者神经功能缺损的影响:多中心随机对照研究 中国针灸2006;26(5):309-312
[51]何扬子;韩冰;胡静;原理;陈卓铭;李静铭;彭菊秀;王丽娜不同留针时间对针刺治疗缺血性中风疗效的影响新中医2005.01.05;37(1):58-60
[52]张玉杰急性缺血性脑卒中择时治疗32例临床研究中医杂志 2004.11.17;45(11):826-828
[53]刘悦;凌方明;蔡高宁;林雪霞;龙目恒头部电针治疗缺血性中风的效应差异中国针灸 2004.08.12;24(8):562-564
[54]杨秋汇头针治疗急性期缺血性中风194例血液流变学观察山西中医2007;23(4):54-56
[55]牛文民;李忠仁CT定位电头针治疗缺血性中风机理研究上海针灸杂志2006;25(7):3-4
[56]李雅洁;张红星;张唐法头针对缺血性脑卒中复发相关因素同型半胱氨酸、纤维蛋白原及抗凝血酶原Ⅲ含量的影响中国临床康复2006;10(23):1-3
[57]季杰;刘慧林;程金莲;王麟鹏三通法针刺对急性缺血性脑血管病患者血清TNF-α及IL-1β的影响中国中西医结合杂志2006;26(6):500-503
[58]陈文;谭敏;梁立安;翁泰来 艾灸足三里、悬钟对缺血性中风脑血管功能的影响及其临床意义中国针灸2006;26(3):161-165
[59]沈卫东;孔敏;张瑞雪 针药结合治疗对缺血性中风患者SOD、MDA影响的临床研究 河南中医学院学报2005.11.20;20(6):36-37
[60]王伟志;王占奎;赵建国;傅立新 针灸对缺血性脑血管病颈动脉粥样硬化患者血脂、血流变、LPO和SOD、ET和CGRP的影响 上海针灸杂志2005.07.25;24(7):19-23
[61]冯淑兰;杨路;古继红;李月梅;赖新生 颓三针与补阳还五汤合用对缺血性脑卒中患者白细胞介素-1β和白细胞介素6的影响 中国康复医学杂志2005.06.26;20(6):453-454
[62]李艳慧;李旅萍;林国华 病灶定位围针治疗缺血性中风的临床观察 广州中医药大学学报2004.09.15;21(5):376-378
[63]齐宇;何春慧;周丹;张福鼎;张彩荣 针灸治疗超早期缺血性中风16例近 期疗效观察 中国冶金工业医学杂志2004.06.15;21(3):191-192
[64]黄文权;唐绪刚;姜利鲲;邓明慧;曹文新 中药、针灸治疗脑卒中后遗症研究进展 中国中医急症 2008;17(1):88-89
[65]孔立红;孙国杰(指导)脑缺血耐受机制及针刺对脑缺血耐受机制可调性展望上海针灸杂志 2005.04.25;24(4):42-46
[66]丁炯;顾振;吴文忠;韩群颖;王鹤鸣;周建平;肖明;马瑞 电针预处理对大鼠局灶性脑缺血的影响 中国临床康复2004.01.05;8(1):106-107
[67]刘喆;赖新生 电针对局灶性脑缺血大鼠神经功能缺损及病理形态的影响中国针灸2005,25(12):879-884
[68.丁春华;刘焕荣;张少丹;凌亦凌 针灸治疗幼鼠缺血缺氧性脑病的实验研究 中国应用生理学杂志2005.11.28;21(4):400-401
[69]卜彦青:杜广中 头体针对脑缺血大鼠脑循环时效关系的实验研究 中医药学报 2004.04.20;32(2):26-27
[70]关玲;石现;杜元灏针刺对脑梗死大鼠脑微循环灌注状态的定性和定量分析中国临床康复 2005.08.07;9(29):238-240
[71]王少军;张立德(指导) 电针刺改善短暂性大脑中动脉梗塞大鼠中枢机能的实验研究 辽宁中医杂志2003.09.18;30(9):750-751
[72]张秀花;孙世晓;徐博佳 井穴点刺出血对局灶性脑缺血大鼠脑梗塞体积影响的基础研究 针灸临床杂志 2004.12.20;20(12):47-48
[73]丁春华;刘焕荣;张少丹;凌亦凌 针灸治疗幼鼠缺血缺氧性脑病的实验研究 中国应用生理学杂志2005.11.28;21(4):400-401
[74]黄碧兰;余良主;刘寿仙;王帮华 “手十二井穴”刺络放血对大鼠局灶性脑缺血后SOD活性和MDA含量的影响 咸宁学院学报·医学版 2005.02.15;19(1):4-6
[75]任玉录;孙德俊 电针对局灶性脑缺血急性期大鼠脑组织中自由基水平影响和神经功能相关性的实验研究 中西医结合心脑血管病杂志2008;6(6):679-681
[76]华金双;李丽萍;朱现民 艾灸预处理对全脑缺血大鼠SOD、MOA的影响 中国针灸 2006;26(8):595-597
[77]李刃;李忠仁;沈梅红;牛文民;林旭明 电针对脑缺血大鼠血清GSH、GSH-Px影响的研究 上海针灸杂志 2006;25(9):40-41
[78]姚凯;郭义;胡利民;曲竹秋 针刺对大鼠脑缺血超早期脑细胞内外游离钙离子浓度的影响 中国中西医结合急救杂志2005.09.28;12(5):303-305
[79]马惠芳;郭长青;邬继红;任秀君;严洁;林磊;金智秀;张露芬;图娅 针刺“水沟”穴与针药结合对实验性全脑缺血大鼠脑组织钙调素活性影响的实验研究 北京中医药大学学报 2003.01.30;26(1):84-85
[80]施昱丞;任秀君;洪银珠;图娅 电针对高血脂合并脑缺血大鼠治疗前后血脂含量变化的影响 中国康复医学杂志2007:22(3):225-229
[81]王述菊;孙国杰;吴绪平;黄伟;丁昀 电针百会、水沟对急性脑梗死大鼠凝血和纤溶系统影响的研究 世界针灸杂志·英文版 2008;18(2):23-27
[82]孙忠人;佘军;吴燕|JING|针刺对急性局灶性脑缺血大鼠血清白蛋白、球蛋白含量及其比率的影响 中国中医药科技2004.09.20;11(5):261-262
[83]杨静;熊利泽:王强;刘艳红 阿片受体在电针预处理诱导大鼠脑缺血耐受效应中的作用 中华老年多器官疾病杂志 2006:5(3):218-221
[84]余晓慧,孙国杰 针刺对局灶性脑缺血大鼠脑细胞凋亡及Bcl-2蛋白表达的影响J.针刺研究,2004,1(29):15-17
[85]卜渊,耿德勤,曾因明.针刺调节脑缺血再灌后细胞凋亡相关基因表达的研究进展J.针刺研究,2003,4(28):288-291
[86]张春红,王舒,郑灏泳,等 针刺对局灶性脑缺血大鼠脑细胞凋亡的影响J.针刺研究,2003,2(26):102-105
[87]高明灿,王淑斌.针刺对缺血缺氧性脑性瘫痪幼鼠脑细胞凋亡及含水量的干预效应J.中医康复研究,2005,9(21):132-133
[88]田代实,邓医宇,王光海,等 针刺预处理对大鼠局灶性脑缺血的抗细胞凋亡作用 J.第四军医大学学报,2004,25(1):27-29
[89]倪金霞;高维滨;朱文增;姜建玲;吴壮项针疗法对急性脑梗死大鼠病理学及bel-2表达的影响 针灸临床杂志2007:23(6):46-47
[90]孙忠人;张力;唐伟;李晓捷;单丽莉:马睿杰 针刺预处理对全脑缺血大鼠脑组织细胞凋亡的影响 中国临床康复2006;10(15):144-145
[91]王秀云;李积胜;郭义;刘公望:潘荣菁;李桂兰;韩煜;王强;张果忠手十二井穴刺络放血法对MCAO模型大鼠大脑皮层c-fos蛋白表达的影响上海针灸杂志2004.23(12):39-41
[92]余晓慧 电针对局灶性缺血大鼠Fas蛋白表达的影响 江西中医学院学报2005.02.15;17.(1):40
[93]余晓慧 电针对局灶性脑缺血大鼠bax蛋白表达的影响 河南中医2005.02.10;25(2):30
[94]余晓慧电针对局灶性脑缺血大鼠c-fos蛋白表达的影响甘肃中医2005.05.15;18(5):41-42
[95]余晓慧 电针对局灶性脑缺血大鼠Caspase-3蛋白表达的影响 辽宁中医学院学报2005.03.18;7(2):167
[96]冉群芳;倪光夏 针刺对脑缺血后细胞凋亡相关基因表达影响的研究进展上海针灸杂志 2007;26(7):46-48
[97]韩冰冰;宋文丽;宋炳玉;王世军 针刺对脑缺血模型动物凋亡相关基因表达影响的研究进展现代中医药 2005.01.25;(1):58-60
[98]霍国敏;周爽;薛茜;石武年 十二井穴刺络放血对局灶性脑缺血模型大鼠神经细胞功能的影响山东中医杂志 2006;25(7):477-478
99]李家康;何伟;刘又香;陈墩寿;张茂林 电针对局灶性脑缺血大鼠脑组织TNF-α和NO含量的影响 中医药学刊2004.02.18;22(2):203-204
[100]洪银珠;任秀君;施昱丞;韩止荣;金智秀;图娅 电针干预对高血脂合并脑缺血大鼠血脂四项及TNF-α含量的影响 针灸临床杂志 2007;23(4):51-55
[101]马惠芳;图娅;马文珠;郭长青;郝晋东:邬继红 “十二井穴”针法对局灶性脑缺血大鼠脑皮质及血清肿瘤坏死因子-α含量的影响 针刺研究 2006;31(1):35-37,42
[102]李忠仁;崔龙;沈梅红;项晓人 电针对脑纹状体缺血性神经元细胞凋亡及基因表达的调整中国临床康复 2006;10(7):105-107
[103]唐伟;王威:孙忠人;张力 针刺预处理全脑缺血大鼠海马CA1区Bcl-2mRNA的表达 中国中医基础医学杂志 2007;13(2):156-158
[104.唐伟;孙忠人;张力;王威 针刺预处理全脑缺血大鼠海马CA1区细胞凋亡和热休克蛋白70mRNA的表达 中国临床康复2005.10.07;9(37):90-92
[105]余晓慧 电针对局灶性脑缺血大鼠热休克蛋白70表达的影响现代 中西医结合杂志 2005.07.20;14(14):1831
[106]王秀云;李积胜;刘公望;郭义;张果忠;潘荣菁;王强;李桂兰;韩煜 井穴刺络放血法对MCAO模型大鼠大脑皮层HSP70蛋白表达的影响 天津中医药2005.22(6):477-479
[107]黄碧兰;程静 “手十二井穴”刺络放血对大鼠局灶性脑缺血后N0含量和NOS活性的影响 咸宁学院学报·医学版2004.10.15;18(5):312-314
[108]黄碧兰;余良主;程静 “手十二井穴”刺络放血对大鼠局灶性脑缺血后一氧化氮合酶活性的干预作用 中国临床康复2006;10(7):174-176
[109]高锋;何伟;陈墩寿;李家康 电针“人中”、“内关”对急性脑缺血大鼠血清一氧化氮的影响 中华现代临床医学杂志2004.01.15;2(1):4-5
[110]郭永明;梁宪如;杜元灏;郭永铁;石学敏 醒脑开窍针法对局灶性脑缺血大鼠脑组织及血清IL-1β含量的影响 上海针灸杂志 2004.08.25;23(8):35-37
[111]曲金柱;李宛青 电针刺激百会及大椎穴对新生鼠缺氧缺血性脑损伤的保护 中国临床康复2005.08.07;9(29):249-251
[112]陈永胜;陈凤琴;赵建新:田元祥 电针对血管性痴呆小鼠脑组织超氧 化物岐化酶、丙二醛及乙酰胆碱酯酶的影响 中国临床康复2005.03.07;9(9):111-113
[113]王世军;崔可密;卢岩;郭继龙;韩冰 针刺对MCAO大鼠海马CA3区微血管数目及神经元死亡率的影响山东中医药大学学报 2005.01.15;29(1):59-60
[114]杨文清;王琦;王俊卿;郭克锋针刺改善慢性全脑缺血缺氧性大鼠认知功能的机理 中国康复2007;22(4):225-227
[115]卢雨微;吕明庄;贺志光耳穴埋针对血管性痴呆大鼠记忆障碍及B淀粉样蛋白表达的影响 中国针灸2006;26(11):804-808
[116]赵宇辉;孙忠人;李晓捷;李蕾 艾灸预处理对全脑缺血大鼠海马CA1区Bcl-2和Bax蛋白表达影响的实验研究 针灸临床杂志2006;22(8):53-54
[117]张慧敏;费宇彤;时宇静;贾宝辉;图娅(指导) 针刺“百会”“太阳”改善局灶性脑缺血脑微血管内皮细胞功能的动态观察 针刺研究2006;31(2):67-72,封3
[118]唐伟;孙忠人;张力;王威:王卓尔;白鹰 针刺预处理全脑缺血大鼠海马CA1区B细胞淋巴瘤2mRNA的表达中国临床康复2006:10(11):123-125
[119]陈振虎:赖新生;江钢辉 电针四神聪穴对实验性血管性痴呆大鼠中枢胆碱能神经元的影响 现代中西医结合杂志2006;15(14):1884-1885
[120]赵慧英;牟萍;董岩 病理条件下的神经可塑性及在针灸研究中的可能应用 针刺研究2008,33(1):41-46
[121]Williams JM,Guevremont D.Kennard JT.et al.Long-term regulation of N-methyl-D-aspartate receptor subunits and associated synaptic proteins following hippocampal synaptic plasticity.Neuroscience.2003.118:1003-1013.
[122]Chetkovich DM,chen L,Stocker TJ,et al.Phosphorylation of the postsynaptic density-95(PSD-95) / discs large / zona occludens-1 binding site of stargazin regulates binding to PSD-95 and synaptic targeting of AMPA receptors.J Neurosci.2002.22:5791-5796.
[123]Schnell E,Sizemore M,Karimzadegan S.et al.Direct interactioas between PSD-95 and stargazin control synaptic AMPA receptor number.Proc Natl Acad Sci USA,2002,99:13902-13907.
[124]Kalia Lv.Salter MW.Interactioas between Src family protein tyrosine kinases and PSD-95.Neuropharmacology.2003.45:720-728.
[125]杜亦旭;许能贵;易玮;黄国新;蔡通;黄真炎;吴玲霓 电针对不同时间段局灶性脑缺血大鼠缺血区突触数密度、面密度的影响 广州中医药大学学报 2008;25(3):224-228
[126]白晶;李宝栋;唐强(指导);邢殿文 头穴丛刺法对急性缺血性脑梗死大鼠神经可塑性影响的实验研究 针灸临床杂志2005.06.15;21(6):47-48
[127]汪帼斌;许能贵;佘世锋;易玮;黄真炎;赖新生 电针对局灶性脑缺血大鼠缺血区突触结构的影响 中国临床康复2005.02.05;9(5):115-117
[128]杨卓欣;于海波;王玲;皮敏;张家维 电针对缺血性脑损伤大鼠海马齿状回突触传递活动的影响 广州中医药大学学报2005.03.15;22(2):118-122
[129]易玮;许能贵;汪帼斌;佘世锋;徐振华;赖新生 电针对局灶性脑缺血大鼠缺血区皮层神经生长因子表达的影响 广州中医药大学学报 2006:23(1):35-38
[130]范郁山;罗燕 浅刺针法对脑梗塞大鼠的脑组织缺血半暗带NGF表达的影响针灸临床杂志2008;24(1):36-38
[131]纪中 电针百会穴对大鼠缺血区脑组织神经生长因子影响的研究 浙江中医学院学报 2005.05.15;29(3):67
[132]许能贵;汪帼斌;佘世锋;易玮;赖新生针刺百会、大椎穴对局灶性脑缺血大鼠皮层脑源性神经营养因子表达的影响 广州中医药大学学报 2004.11.15;21(6):439-442
[133]胡圣望;胡勇;胡亚林:吴红年 新生大鼠脑缺血缺氧后脑组织脑源性神经营养因子表达及电针的干预效应 中国临床康复2006;10(35):84-86
[134]蒋红芝:黄光英;张明敏 针刺对局部脑缺血大鼠血管内皮生长因子表达和脑血流的影响 微循环学杂志2006;16(2):9-11,封2
[135]李宝栋;王志勇;白晶;白海娟;公维志;闫瑞萍;刘振江;王利春 头穴丛刺对大鼠缺血脑组织血管内皮生长因子表达的影响 世界针灸杂志·英文版2008:18(1):38-44
[136]李红颖;朱文增;东贵荣;王凤军:客蕊 头穴透刺对急性脑梗死大鼠神经丝蛋白-200的影响上海针灸杂志 2007;26(8):40-42
[137]李红颖;朱文增;东责荣;王凤军;客蕊;崔学军(翻译) Influence of Scalp Point-through-point Acupuncture on 200 kDa Neurofilament Protein in Rats with Acute Cerebral Infarction 针灸推拿医学·英文版 2007;5(6):341-344
[138]钱长晖;毛庆菊;王芳;吴艳;刘冠男;罗涛 电针对大鼠脑缺血海马损伤区神经元δ-连环素表达的影响 福建医药杂志2007;29(2):82-84
[139]杨卓欣;于海波;饶晓丹:刘远声;皮敏 任脉电针对脑缺血大鼠侧脑室下区神经干细胞增殖与分化的影响 中医杂志 2006;47(6):429-432
[140]张慧敏 头穴针刺对局灶性脑缺血大鼠脑微血管内皮第八因子相关抗原影 响的动态观察 中国康复医学杂志2006;21(4):289-292
[141]李铁浪;严洁;邓常青;沈菁;胡蓉;王灵 电针不同穴组对急性脑缺血大鼠脑组织NPY及其基因表达的影响 湖南中医学院学报2006:26(2):43-45
[142]胡俊;李玲;张海鸥;吴军 脑缺血后可逆性蛋白磷酸化水平变化及电刺激对其的影响 中西医结合心脑血管病杂志2006;4(7):603-606
[143]耿战辉,程义勇 重新认识神经胶质细胞 生理科学进展.2003,34(3):231-234
[144.陈明明;成泽东;陈以国(指导) 论小胶质细胞在针灸治疗缺血性脑病研究中的新思路 中医药学刊2005.09.15;23(9):1629-1630
[145]罗燕,许能贵,易玮,杜亦旭.电针对局灶性脑缺血大鼠缺血灶周围区星形胶质细胞谷氨酸转运体的影响.安徽中医学院学报.2009,28(1):30-33
[146]谭峰:万赛英;王海侨 电针对轴突生长与抑制因子的干预 中国临床康复2006;10(23):152-154
[147]刁利红;杨卓欣;罗文舒电针任脉联合bFGF对脑缺血大鼠ERK通路的调节作用 中医药信息2006;23(3):17-20
[148]呙登俊;赵永波;陈英辉 针刺对缺血性脑损伤大鼠的治疗作用及对GDNF 表达水平和MAPKs信号转导通路的调节 神经科学通报·英文版 2005.11.30;21(6):385-390
[149]陈泽斌;王华 针刺对大鼠脑组织神经生物学基因表达的研究 中国针灸2005.08.12;25(8):573-576
[150.曾俊:严洁(指导) 针灸对急性期脑缺血保护作用机制研究进展 中医药导报2008:14(1):72-75
[151]Robert F Thamas M.Rapid ischemic cell death in immature oligodendrocytes:a fetal glutamate release feed back loop[J].Neuroscience,2000,20(1):34-42.
[152]Nitatori T,Sato N,Waguri S,et al.Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis[J].Neurosci,1995,15(2):1001-1011.
[153]Sun JJ,Liu Y,et al.Effects of P2Y1 receptor on glial fibrillary acidic protein and glial cell line-derived neurotrophic factor production of astrocytes under ischemic condition and the related signaling pathways.Neurosci Bull.2008;24(4):231-43.
[154]Shyu WC,Lin SZ,et al.Secretoneurin promotes neuroprotection and neuronal plasticity via the Jak2/Stat3 pathway in murine models of stroke.J Clin Invest.2008;118(1):133-48.
[155]Ihle JN.STATs:Signal transducers and activators of transcription [J],Cell,1996,84(3):331-334.
[156]Pellegrini S,Dusanterfourt I.The structure,regulation an d function of the Janus kinases(JAKs)and the signal transducers and activators of transcription(STATs)[J].Eur J Biochem,1997,248(3):615-633.
[157]Kisseleva T,Bhattacharya S,Braunstein J,et al.Signaling through the JAK-STAT pathway:recent advances and future challenges[J].Gene,2002,285(1):1-24.
[158]Planas AM,Soriano MA,et al.Induction of Stat3,a signal transducer and transcription factor,in reactive microglia following transient focal cerebral ischaemia.Eur J Neursci,1996,8(12):2612-2618.
[159]李文涛等 慢性脑缺血对信号转导和转录激活因子-1的表达 中国实用神经疾病杂志2007:10(3):82-83
[160]李洪春:马萍等 脑缺血/再灌注诱导大鼠信号转导与转录激活子-1的变化 中华医学研究杂志2006:6(5):484-486
[161]Takagi Y,Harada J,Chiarugi A,et al.STATI is activated in neurons after ischemia and contributes to ischemic brain injury[J].J Cereb Blood FlowMetab,2002,22(I1):1311-1318.
[162]Justicia C.Gabriel C,et al.Activat ion of the JAKS/STATS pathway following transient focal cerebral ischemia:signaling thigh Jakl and STAT3in astrocytes.Glia,2000,30:253-270.
[163]Wen TC,Peng H,Hata R,et al.Induction of phosphorylated-STAT3following focal cerebral ischemia in mice.Neurosci Lett,2001,303(3):153-56.
[164]谢惠芳 刘振华 朱利元 大鼠脑缺血再灌注损伤后脑组织STAT3变化的免疫组织化学研究 临床神经病学杂志2000.12.25:13(6):329-331
[165]Satriotomo I,Bowen KK,Vemuganti R.JAK2 and STAT3 activation contributes to neuronal damage following transient focal cerebral ischemia.J Neurochem.2006;98(5):1353-68.
[166]Yamashita T,Sawamoto K,Suzuki S,et al.Blockade of interlrukin-6sign aling aggravates ischem ic cerebral damage in m ice:possibleinvolvement of STAT3 activation in the protection of neurons[J]JNeurochem,2005,94(2):459-468.
[167]Dziennis S,Alkayed NJ Role of signal transducer and activator of transcription 3 in neuronal survival and regeneration.Rev Neurosci.2008;19(4-5):341-61.)
[168]苟俊 潘峰等 低氧状态下海马神经元细胞信号转录因子和活化子3,5的基因表达状况 中国临床康复2004.01.05:8(1):66-67
[169]Chong ZZ,Kang JQ,Maiese K.Hematopoietic factor erythropoietin fosters neuroprotection through novel signal transduction cascades.J Cereb Blood Flow Metab.2002:22(5):503-14.
[170]苑晓玲 细胞因子信号转导负调控蛋白-SOCS家族研究进展 国外医学·内分泌学分册2001,21(2):83-85
[171]许能贵,易玮,马勤耘等.电针对大鼠局灶性脑缺血后神经元损伤保护作用的研究.中国针灸,2000;20(4):237-240。
[172]陈忠义;张发荣;李寅超 浅谈中医对血管性认知障碍的认识 辽宁中医药大学学报2007:9(2):33-34.
[173]韩济生主编.神经科学纲要.北京医科大学、中国协和医科大学联合出版社,1993.723-736..
[174]Yonemori F,Yamaguchi T,Yamada H,et al.Spatial cognitive performance after chronic focal ischemia in ratsJ..J Cereb Blood Flow Metab,1999,19(5):483-94.
[175]谢集建 缺氧缺血性脑损伤对学习记忆的影响及其机制研究进展 国外医学·妇幼保健分册2001,12(2):83-85.
[176]曹新生 孙喜庆 吴兴裕 实验性脑缺血性损伤与学习记忆功能 中华航空航天医学杂志2005,16(2):157-160.
[177]谢集建.缺氧缺血性脑损伤对学习记忆的影响及其机制研究进展.国外医学妇幼保健分册,2001,12(2):83--85.
[178]Wen TC,Matsuda S,Yoshimuro H,et al.Ciliary neurotropic factor prevents ischemia induced learning disability and neuronal loss in gerbilsJ.Neurosci Lett.1995,19:55-58.
[179]Araki T,Kato H,Kogure K.Selective neuronal vulnerability following transient cerebral ischemia in the gerbil:distribution and time course.Acta Neurol Scand,1989,80(6):548-553.
[180]Briones TL,Therrien B.Behavioral effects of transient cerebral ischemia.Bio Res Nurs,2000,1(4):276-286.
[181]谢集建,常燕群,陈宝芳,等.新生大鼠缺血低氧性脑损伤后学习记忆和海马神经元超微结构的研究.中华急诊医学杂志,2001,10(3):155-157.
[182]姚国恩,王景周,陈曼娥,等.血管性痴呆大鼠海马区长时程增强变化的研究.中国行为医学科学,2002,11(4):368-370.
[183]Rison R A,Stanton P K.Long-term potentiation and N- methyl-D-aspartate receptors:foundation of memory and neurologic diseaseJ.Neurosci-biobehav-rev.1995,19(4):533-552.
[184]Lyubkin M.Duzand DM,Haxhiu MA.Interaction between tetanus Long - term potentiation and hypoxia - induced potentiation in the rat hippocampusJ..Neurophysiol,1997,78(5)2475-2482.
[185]Hsu KS,Huang CC.Characterization of the anoxia-induced Long-terln synaptie potentiation in area CAlot the rat hippocampusD.British J of Pharmcol,1997,i22:671-681.
[186]沈维高,何欣,冯利民,等.老年大鼠在空间辨别性学习记忆时海马Ach 和Ach能纤维的变化J.中国老年学杂志,2006,26(11):1528-1529.
[187]Dunbar GL,Rylett RJ,Schnidt BM,et al.Hippocampal choline acetyltransferase activity correlates with spatial learning in aged ratsJl.Brain Res,1993,604:266-272.
[188]张军艳,张博爱,朱红灿,黄晓琳 学习记忆训练对全脑缺血大鼠认知能力的影响及其胆碱能机制 中国康复医学杂志,2008,23(4):305-308.
[189]Nagakura A,M iyake TK,Takagi N,et al.Impairment of adenylyl cyclase and of spatial memory function after microsphere embolism in rats.J Neurosci Res,2002,68(3):363-372.
[190]Nagakura A,Takagi N,Takeo S.Im pairment of cerebral cAMP-mediated signal transduction system and of spatial memory function after microsphere embolism in rats.Neuroscience,2002,I13(3):519-528.
[191]姚国恩,王景周,陈曼娥.血管性痴呆大鼠认知障碍的N-甲基D-天冬氨酸受体机制.中国临床康复,2003,7(10):1496-1498.
[192]张雪朝,吕明庄,贺志光,等针刺对VD大鼠记忆障碍及c-fos mRNA和蛋白表达的影响.中国康复医学杂志,2001,16(2):74-76.
[193]张雪朝,贺志光,吕明庄,等.血管性痴呆大鼠记忆障碍与海马Bcl-2蛋白表达的研究.中国病理生理杂志,2002,18(10):1294-1295.
[194]王黎,赖新生,雷娓娓电针对全脑缺血大鼠学习记忆能力和海马神经元超微结构的影响中国针灸2002,22(1):47-50.
[195]闫兵;许能贵;唐纯志;何利雷;绍瑛 电针对血管性痴呆大鼠学习记忆能力的改善作用及其机理探讨 广州中医药大学学报2007:24(3):215-218
[196]卢雨微;吕明庄;贺志光 耳穴埋针对血管性痴呆大鼠记忆障碍及β淀粉样前体蛋白表达的影响 上海针灸杂志 2007:26(5):44-46
[197]张玲 张为众 针刺对反复短暂脑缺血再灌注大鼠脑损伤的影响 中国老年学杂志2007,12(2.:2387-2389.
[198]许能贵:易玮:马勤耘:许冠荪:朱舜丽:陈全珠 电针对大鼠局灶性脑缺血后神经元损伤保护作用的研究 中国针灸2000.04.12:20(4):237-240
[199]许能贵:易玮;赖新生;靳瑞电针对局灶性脑缺血大鼠脑细胞内Ca2+含量的影响 中国中西医结合杂志2002.04.20;22(4):295-297
[200]骆仲达;骆仲逵;许能贵;赖新生电针对局灶性脑缺血大鼠脑源性神经营养因子影响的研究 针刺研究2002.06.15:27(2):105-107
[201]骆仲达:赖新生(指导):许能贵 电针督脉对缺血性脑损伤大鼠神经细胞凋亡的影响 安徽中医学院学报2002.12.01;21(6):27-29
[202]骆仲达;骆仲逵;许能贵;赖新生电针对局灶性脑缺血大鼠缺血区脑组织神经细胞凋亡及神经生长因子影响的研究 针刺研究2002.09.15;27(3):165-169
[203]汪帼斌;许能贵;佘世锋;易玮;黄真炎;赖新生 电针对局灶性脑缺血大鼠缺血区突触结构的影响 中国临床康复2005.02.05:9(5):115-117
[204]徐振华(1);许能贵(2);易玮(2);靳瑞(2)脑缺血大鼠缺血同侧海马齿状回突触可塑性的变化中国临床康复2006;10(19):37-40
[205]徐振华;许能贵;易玮;靳瑞 脑缺血大鼠缺血同侧海马齿状回突触可塑性的变化 中国临床康复2006;10(19):37-40
[206]徐振华;许能贵;易玮;符文彬;靳瑞 针刺对大鼠脑缺血后海马突触可塑性的促进作用 安徽中医学院学报2007;26(3):18-23
[207]易玮;许能贵;汪帼斌;徐振华;余世锋;黄真炎;赖新生 电针对局灶性脑缺血大鼠突触可塑性促进作用的实验研究 中国中西医结合杂志2006:26(8):710-714
[208]杜亦旭;许能贵;易玮;黄国新;蔡通;黄真炎;吴玲霓 电针对不同时间段局灶性脑缺血大鼠缺血区突触数密度、面密度的影响 广州中医药大学学报2008;25(3):224-228
[209.胡镜清,温泽淮,赖世隆等Morris术迷宫检测的记忆属性与方法学初探广州中医药大学学报2000,17(2):117-1 19.
[210]Block F.Global ischem ia and behavioural deficits.Prog Neurobiol,1999,58(3):279-295.
[211]尹军祥 田金洲 程龙 时晶 等MCAO模型大鼠学习记忆特征中国行为医学科学2006年3月第15卷第3期197-199.
[212]姚国恩,王景周,陈曼娥,等.血管性痴呆大鼠海马区长时程增强变化的研究 中国行为医学科学,2002,11(4):368-370.
[213]曹贵方 杨期东JAK-STAT信号转导途径与脑缺血 国外医学神经病学神经外科学分册2004,31(4):340-343.
[214]Wagner FD,Buz S,Knosalla C,et al.Modulation of circulating endothelin-1 and big-endothelin by nitric oxide inhalation following left ventricular assist device implantationJ..Circulation,2003,108(Suppl 1):278-284.
[215]Amana CV,Grammatikakis N,Chernov M,et al.Regulation of c-myc expression by IFN -through Statl dependent and independent pathwaysJ..EM BO J,2000,19(2):263-272
[216]谢惠芳 徐如祥 姜晓丹JAKs-STATs信号转导通路与缺血性脑损伤 中华神经医学杂志2006,5(10):1071-1072,1075
[217]曹贵方 杨期东JAK-STAT信号转导途径与脑缺血 国外医学神经病学神经外科学分册2004,31(4):340-343
[218]Suzuki S,Tanaka K,Nngawa S.et al.Phospharylatian of signal transducer and activators of transcription-3(stat3) after focal cerebral ischemia in rats.Exp Neurol.2001.170:63-71.
[219]Choi JS,Kim SY,Cha JH,et al.Upregulation of gp130 and STAT3activation in the rat hippocampus following transient forebrain ischemia.Glia,2003,41(3):237-246.
[220]Li H,Zhang Q,Zhang G.Signal transducer and activator of transcription-3 activation is mediated by N-methyl-D-aspartate receptor and L-type voltage-gated Ca~(2+)channel during cerebral ischemia in rat hippocampus.Neuronsci Lett,2003,345(1):61-64.
[221]Byts N,Samoylenko A,Fasshauer T,Ivanisevic M,Hennighausen L,Ehrenreich H,Siren AL.Essential role for Stats in the neurotrophic but not in the neuroprotective effect of erythropoietin.Cell Death Differ.2008Apr;15(4):783-92.Epub 2008 Feb 8.