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

doi:10.3969/j.issn.1006-7795.2015.03.016

首都医科大学学报 ›› 2015, Vol. 36 ›› Issue (3): 420-425.doi: 10.3969/j.issn.1006-7795.2015.03.016

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

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

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

收稿日期:2014-11-20 出版日期:2015-06-21 发布日期:2015-06-15
通讯作者: 王雅丽 E-mail:zhaohui8957@sina.com
基金资助:
国家自然科学基金(81370482, 31400991),北京市自然科学基金 (7132017), 北京市属高等学校创新团队建设与教师职业发展计划项目 (IDHT20140514).

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

Zhang Ning^1,2,3, Wu Xi⁴, Wang Shuo⁴, Wang Lei⁵, Zhang Qiuxia⁵, Zhao Hui⁵, Wang Yali⁵

1. Neuropsychiatry&Behavioral Neurology and Clinical Psychology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China;
2. China National Clinical Research Center for Neurological Diseases, Beijing 100050, China;
3. Center of Stroke, Beijing Institute for Brain Disorders, Beijing 100050, China;
4. Neurology Department Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China;
5. Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China

Received:2014-11-20 Online:2015-06-21 Published:2015-06-15
Supported by:
This work was supported by the National Natural Science Foundation of China (81370482 and 31400991),Natural Science Foundation of Beijing(7132017), the Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges under Beijing Municipality (IDHT20140514).

摘要/Abstract

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(cystein-aspartate protease-3,Caspase-3)、淀粉样前体蛋白(amyloid precursor protein,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.

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

Abstract:

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 15d 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-3 was 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 Aβ42. As a result, Xiaoshuan enteric-coated capsule can protect the thalamus of ischemia.

Key words: Xiaoshuan enteric-coated capsule, cerebral ischemia, cystein-aspartate protease-3, amyloid precursor protein, β-amyloid protein

中图分类号:

R741

张宁, 吴曦, 王铄, 王蕾, 张秋霞, 赵晖, 王雅丽. 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[J]. 首都医科大学学报, 2015, 36(3): 420-425.

Zhang Ning, Wu Xi, Wang Shuo, Wang Lei, Zhang Qiuxia, Zhao Hui, Wang Yali. Effects of Xiaoshuan enteric-coated capsule on neuronal damage by eliminating β-amyloid protein in thalamus of MCAO rats[J]. Journal of Capital Medical University, 2015, 36(3): 420-425.

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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

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