基于血清蛋白组学初步探讨脑心通胶囊防治心脑血管疾病的作用机制  

Preliminary investigation on mechanism of Naoxintong capsule's preventive treatment of cardio-cerebrovascular disease based on serum proteomics

作　　者：耿潇[1] 陈璐[1] 赵步长 李春晓[1] 邱丽珍[1] 尤星宇 王益民 张璐莎 王虹[1] 

机构地区：[1]天津中医药大学中医药研究院天津市现代中药重点实验室天津市中药药理学重点实验室,天津300193 [2]陕西步长制药有限公司,陕西西安712000

出　　处：《中国中药杂志》2016年第15期2864-2871,共8页China Journal of Chinese Materia Medica

基　　金：新世纪优秀人才支持计划项目(NCET-13-0935);国家自然科学基金项目(81173592);国家国际科技合作专项(2015DFA30430);长江学者和创新团队发展计划项目(IRT1276)

摘　　要：步长脑心通胶囊具有益气活血,化瘀通络的作用,临床广泛用于冠心病、心绞痛、脑卒中等心脑血管疾病的治疗,其预防的药效物质基础及可能作用机制尚不明确。该实验取C57BL/6小鼠20只,雌雄各半,按体重随机分为对照组(生理盐水)和脑心通组。适应性喂养7 d后开始给药,连续灌胃3 d,末次给药后1 h,心尖取血,每组取6只制备血清蛋白样品,进行双向凝胶电泳,图像分析,质谱检测,筛选并鉴定差异表达蛋白,对差异蛋白进行生物信息学分析。脑心通胶囊给药组与对照组差异表达蛋白24个,其中与对照组相比,上调12个,下调12个。差异蛋白所参与的通路涉及细胞凋亡信号通路,血管内皮生长因子信号传导通路等,其中vasohibin-1是血管生成的负反馈调节因子,Western blot结果证实脑心通胶囊可使vasohibin-1蛋白表达降低,与双向电泳结果一致。脑心通胶囊给药组血清蛋白表达有差异,差异蛋白的主要作用靶位为内皮细胞、炎症细胞及血小板等,这些蛋白的改变提示脑心通胶囊在一定程度上可以改善冠心病及缺血性脑血管疾病,为脑心通胶囊未病先防的分子机制研究提供了潜在的生物标志物。Naoxintong capsule has beneficial effects for activating blood circulation, dispersing blood stasis and dredging collateral. It is widely used in the treatment of coronary heart disease, angina pectoris, stroke and cardiovascular disease. However, the pharma- codynamic basis and possible mechanism of its preventive effects are not clear. In this study, 10 male and 10 female C57BL/6 mice were used, and were randomly divided into the control group （saline） and Naoxintong group. Adaptively fed for 7 days in common con- ditions, mice were given Naoxintong capsule or saline for 3 days via intragastric administration. Serum was collected from 6 mice in each group 1 h after the last administration. Serum proteins were prepared to do two-dimensional gel electrophoresis. Then image analy-sis and mass spectrometry detection were carried out to screen and identify the differentially expressed proteins and make bioinformatics analysis. It was found that 24 differentially expressed proteins between Naoxintong group and control group. Compared with the control group, 12 proteins were increased, and 12 were decreased. The proteins were involved in apoptosis signal pathway and vascular endo- thelial growth factor signal transduction pathway, in which vasohibin-1 is a negative feedback regulation factor in angiogenesis. Western blot showed that the expression of vasohibin-1 in Naoxintong group was reduced, which is consistent with the result in two-dimensional electrophoresis. Serum proteins expression is different between Naoxintong and control groups. The targets of these differentially ex- pressed proteins include endothelial cells, inflammatory cells and platelets. The changes on proteins showed that Naoxintong capsule may ameliorate coronary heart disease and ischemic cerebrovascular disease, and provide potential biological markers to prevent ische- mic disease.

关 键 词：脑心通胶囊 血清蛋白组学 双向凝胶电泳 

分 类 号：R285.5[医药卫生—中药学]