他克莫司对脑缺血大鼠学习记忆功能的影响及其机制分析  

Effect of Tacrolimus on Learning and Memory of Rats with Cerebral Ischemia and Underlying Mechanisms

作　　者：张丽藏 李文杰 李若禹 闫彩珍[2] 苏素文[2] 王可欣 Zhang Licang;Li Wenjie;Li Ruoyu;Yan Caizhen;Su Suwen;Wang Kexin(The Second Hospital of Hebei Medical University,Shijiazhuang 050005,China;Department of Pharmacology,School of Basic Medical Sciences,Hebei Medical University;The Third Hospital of Hebei Medical University)

机构地区：[1]河北医科大学第二医院,石家庄050005 [2]河北医科大学基础医学院药理教研室 [3]河北医科大学第三医院

出　　处：《中国药师》2021年第3期432-437,共6页China Pharmacist

基　　金：河北省中医药管理局项目(编号:2020167)。

摘　　要：目的:探讨他克莫司对颈总动脉结扎所致脑缺血大鼠学习和记忆功能的影响及机制分析。方法:80只SD大鼠随机分为5组:假手术组、模型组、他克莫司低、中、高剂量组(0.2,1,5 mg·kg^(-1)),每组16只。采用双侧颈总动脉结扎的方法制备大鼠脑缺血模型,手术前后灌胃给药,3 d后进行相关指标检测。Morris水迷宫测定大鼠的学习记忆能力;苏木素-伊红(HE)染色观察海马CA1区病理形态学改变;Western Blot技术检测聚合态和解聚态肌动蛋白(F-/G-actin)、脑发育蛋白(F-/G-drebrin)及钙调磷酸酶(CN)的表达。结果:水迷宫结果显示:与假手术组相比,模型组潜伏时间明显延长(P<0.01),但穿越平台次数无显著差异(P>0.05);他克莫司中、高剂量组较模型组潜伏时间明显减少且高剂量组穿越平台次数明显增加(P<0.05)。HE染色结果显示:模型组较假手术组细胞排列分散,破裂较多;他克莫司中剂量组细胞形态较完整,排列也较为整齐和紧致。Western Blot结果显示:模型组较假手术组F-actin、F-drebrin、F-drebrin/G-drebrin明显降低,G-actin、G-drebrin、CN水平明显升高(P<0.05)。与模型组比,他克莫司中、高剂量组F-actin、F-drebrin、F-drebrin/G-drebrin明显升高,G-actin、G-drebrin、CN水平明显降低(P<0.05)。结论:颈总动脉结扎导致大鼠脑缺血,大鼠的学习记忆能力下降,他克莫司可改善大鼠脑缺血后学习记忆能力,其作用机制可能与增加F-drebrin表达,抑制CN表达和海马肌动蛋白重构有关。Objective: To investigate the effect of tacrolimus on learning and memory in cerebral ischemic rats induced by bilateral common carotid artery ligation and underlying mechanism.Methods: Totally 80 SD rats were randomly divided into 5 groups: sham operation group,model group,tacrolimus low,medium and high dose groups(0.2,1,5 mg·kg^(-1)) with 16 rats in each group.Corresponding drug was administered before and after the operation by gavage,and relevant indicators were tested 3 days later.Morris water maze was used to measure the learning and memory ability of rats;hematoxylin-eosin(HE) staining was used to observe the pathomorphological changes in hippocampal CA1 area;Western blot was used to detect the expressions of polymerized and depolymerized actin(F-/G-actin),brain development protein(F-/G-drebrin) and calcineurin(CN).Results: Compared with that in the sham operation group,the latency time of model group was much longer in the moddel group(P<0.01),while there was no significant difference in the number of crossing the platform(P>0.05).Compared with that in the model group,the latency time of medium and high dose tacrolimus groups was significantly decreased,and the number of crossing the platform in the high dose group was evidently increased(P<0.05).The results of HE staining showed that the cells in the model group were more dispersed and ruptured than those in the sham group.The cell morphology of tacrolimus medium dose group was more complete,and the arrangement was also more orderly and compact.Compared with those in the sham group,the expressions of F-actin,F-drebrin and F-drebrin/G-drebrin in the model group were evidently decreased,and G-actin,G-drebrin and CN were significantly increased(P<0.05).Compared with those in the model group,the expressions of F-actin,F-drebrin and F-drebrin/G-drebrin in tacrolimus medium and high dose groups were significantly increased,and G-actin,G-drebrin and CN were significantly reduced(P<0.05).Conclusion: Tacrolimus can improve the learning and memory ability of rats

关 键 词：他克莫司 脑缺血 学习记忆功能 脑发育蛋白 肌动蛋白 钙调磷酸酶蛋白 

分 类 号：R965.1[医药卫生—药理学]