川芎嗪联合缺血预处理对沙鼠前脑缺血后学习记忆功能及HSP70表达的影响

Effect of Tetramethylpyrazine and ischemic preconditioning on expression of HSP70 and learning-memory capacity of gerbils after cerebral ischemia

目的:研究川芎嗪联合脑缺血预处理对沙鼠前脑缺血再灌后学习记忆及HSP70表达的影响.方法:80只蒙古沙鼠随机分成对照组、前脑缺血组、脑缺血预处理、川芎嗪+脑缺血预处理组,每组20只动物.参照Kirino法制备脑缺血预处理动物模型.术后第3～7日对沙鼠的学习记忆功能进行评定(4-PTT旱路迷宫法),HE染色方法观察海马CA1区神经元形态变化,免疫组化法和Western-blot法检测HSP70的表达,TUNEl法标记神经细胞凋亡数,各取均值.结果:与对照组比较,脑缺血后沙鼠的学习记忆能力下降、海马CA1区存活神经元密度降低、HSP70表达水平增加,神经细胞凋亡数量增多(P<0.05);与脑缺血组比较,缺血预处理组和川芎嗪联合组中沙鼠的学习记忆能力得到改善、存活神经元密度增加、凋亡神经细胞数量回降、HSP70表达水平进一步增加,且上述改变在川芎嗪联合组中更加明显(P<0.05).结论:川芎嗪可增强缺血预处理诱导的脑缺血耐受作用,二者联合应用进一步改善前脑缺血沙鼠的学习记忆能力.其机制可能与协同增强HSP70表达,减少神经细胞的凋亡有关.

AIM ：To study the effect and the possible protective mechanism of TMP （ Tetramethylpyrazine ） combined with ischemic preconditioning on learning-memory function after orebrain ischemiareperfusion injury in gerbils. METHODS： Gerbils （n = 80 ） were divided randomly into 4 groups： control group, ischemia group, ischemia preconditioning group （ IP ）, ischemia preconditioning ＋ TMP treatment group. Transient forebrain isehemia model was formed by bilateral common carotid artery occlusion according to the description of Kifino＇s method. On 3 -7 d after operation, learning-memory function were performedwith 4-PTT dry path maze. Changs of neuron morphons in hippoeampal CA1 region were observed by HE staining. The expression levels of HSP70 were detected by immunohistoehemistry and western Blot. Neurons apoptosis were detected by TUNEL method. RESULTS： Compared with control group, there were higher learning -memory function defect, lower density of survival neurons, more apoptotic neurons and higher expression levels of HSP70 in ischemia group （ P 〈 0.05 ） ; Compared with isehemia group, there were lower learning-memory function defect, higher density of survival neurons, fewer apoptotic neurons and more higher expression levels of HSP70 in IP group and IP ＋ TMP treatment group. What＇s more, the above mentioned indexes changed more significantly in IP ＋ TMP treatment group （ P 〈 0. 05 ）. CONCLUSION： TMP can enhance the effeet of isehemie tolerance induced by ischemic preconditioning. TMP combined with IP can further improve the learning-memory function after forebrain ischemia-reperfusion damage in gerbils. One of molecular mechanisms is related to their cooperative regulation effects on HSP70 expression and reducing neurons apoptosis.