消栓肠溶胶囊清除β-淀粉样蛋白对大脑中动脉栓塞大鼠丘脑神经元损伤的影响  

Effects of Xiaoshuan enteric-coated capsule on neuronal damage by eliminating β-amyloid protein in thalamus of MCAO rats

作　　者：张宁[1,2,3] 吴曦[4] 王铄[4] 王蕾[5] 张秋霞[5] 赵晖[5] 王雅丽[5] 

机构地区：[1]首都医科大学附属北京天坛医院神经精神与临床心理科,北京100050 [2]国家神经系统疾病临床医学研究中心,北京100050 [3]北京脑重大疾病研究院脑卒中研究所,北京100050 [4]首都医科大学附属北京天坛医院神经内科中心,北京100050 [5]首都医科大学中医药学院中医络病研究北京市重点实验室,北京100069

出　　处：《首都医科大学学报》2015年第3期420-425,共6页Journal of Capital Medical University

基　　金：国家自然科学基金(30973782;81473745);北京市自然科学基金(7122018);北京市属高等学校高层次人才引进与培养计划-长城学者项目(CIT&TCD20140329);北京市属高等学校人才强教深化计划"中青年骨干人材培养计划"项目(PXM2011014226)~~

摘　　要：目的观察消栓肠溶胶囊对大脑中动脉栓塞大鼠丘脑神经元损伤以及凋亡蛋白半胱氨酸-天冬氨酸蛋白酶-3(cysteinaspartate protease-3,Caspase-3)、淀粉样前体蛋白(amyloid precursorprotein,APP)、β-淀粉样蛋白(β-amyloid protein,Aβ)表达的影响。方法线栓法建立大脑中动脉栓塞模型,雄性Sprague-Dawley(SD)大鼠采用数字表法随机分成假手术组、模型组、消栓肠溶胶囊(420、140、47 mg·kg^(-1))组、阳性对照药银杏叶提取物(28 mg·kg^(-1))组,连续灌胃给药15 d,每天给药1次。术后15 d采用苏木素-伊红染色染色法观察神经元损伤;采用免疫荧光染色结合图像分析技术检测Caspase-3的表达;采用免疫组织化学染色结合图像分析技术检测APP、Aβ42的表达。结果与假手术组比较,中动脉栓塞模型组大鼠丘脑神经元计数明显减少,Caspase-3阳性细胞数明显增多,APP、Aβ42阳性表达增强,差异具有统计学意义(P<0.01);与模型组比较,消栓肠溶胶囊各剂量能使大鼠丘脑神经元计数增多,Caspase-3阳性细胞数减少,APP、Aβ42阳性表达减弱,差异具有统计学意义(P<0.05);与模型组比较,银杏叶提取物也可明显增多大鼠丘脑神经元计数,减少Caspase-3阳性细胞数,减弱APP、Aβ42阳性表达,差异具有统计学意义(P<0.01)。结论消栓肠溶胶囊可通过保护丘脑区神经元,抑制Caspase-3信号分子激活,抑制APP表达、减少Aβ形成,从而保护缺血丘脑区。Objective To investigate the effects of Xiaoshuan enteric-coated capsule on neuronal damage and the expression of cystein-aspartate protease-3（Caspase-3）,amyloid precursor protein（APP）and β-amyloid protein（Aβ）in thalamus of middle cerebral artery occlusion（MCAO）rats.Methods The animal model of middle cerebral artery occlusion（MCAO）were adopted.Xiaoshuan enteric-coated capsule（420、140、47 mg·kg-1）was given orally to rats once each day for 15 days after ischemia.The expression of Caspase-3 was detected by using immunofluorescence and APP,Aβ42 were detected by using immunohistochemistry at 15 d after ischemia.Results Compared with control rats,the number of neurons was reduced and the number of Caspase-3 was added,the expression of APP and Aβ42 was increased in MCAO rats（P〈0.01）;The number of neurons was added and the number of Caspase-3was reduced,the expression of APP and Aβ42 was decreased in Xiaoshuan enteric-coated capsule rats to compared with the model group（P 〈 0.05）.Conclusion Xiaoshuan enteric-coated capsule increased the number of neurons,reduced the number of Caspase-3 and decreased the expression of APP and Ap42.As a result,Xiaoshuan enteric-coated capsule can protect the thalamus of ischemia.

关 键 词：消栓肠溶胶囊 脑缺血 半胱氨酸-天冬氨酸蛋白酶-3 淀粉样前体蛋白 Β-淀粉样蛋白 

分 类 号：R741[医药卫生—神经病学与精神病学]