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J Proteome Res:中科院生化细胞所黄超兰研究员揭示中药复方药物疏风解毒胶囊治疗急性肺损伤的

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摘要 : 2017年9月8日,国际知名杂志《Journal of Proteome Research》在线发表了中国科学院博狗官方网站首页化学与细胞博狗官方网站首页学研究所国家蛋白质科学研究黄超兰研究员与天津中医药研究院张铁军研究员、复旦大学陶振钢医生的合作成果
2017年9月8日,国际知名杂志《JouRNAl of Proteome Research》在线发表了中国科学院博狗官方网站首页化学与细胞博狗官方网站首页学研究所国家蛋白质科学研究黄超兰研究员与天津中医药研究院张铁军研究员、复旦大学陶振钢医生的合作成果,论文题为“Therapeutic Mechanism Studies of ShuFengJieDu Capsule on an Acute Lung Injury Animal Model Using Quantitative Proteomics Technology” 。研究通过多层次中药复方的分析方法结合定量蛋白组学技术,揭示了疏风解毒胶囊治疗大鼠模型急性肺损伤(ALI, Acute Lung Injury)中的潜在的分子作用机制。复旦大学陶振钢医生为论文第一作者,黄超兰研究员为共同通讯作者。 随着传统中医药的发展,以及社会对中药复方的处方科学性、生产工艺的合理性、质量标准的规范化及中成药质量稳定性等方面要求的逐渐提高,十三五规划将推进中医药现代化列为重点内容,提出要以临床实践为基础,阐释中医药核心理论的科学内涵和博狗官方网站首页基础,阐明中药系统思维模式并丰富发展中医药理论体系的要求。但是长期以来,由于中药复方成分复杂,有效成分较难确定,疗效标准不唯一的特点,严重阻碍了中医药的国际化发展道路。 研究人员结合疏风解毒胶囊的中药药性理论,通过UPLC/Q-TOF-MS整合NF-κB双荧光素酶报告博狗官方中文德州扑克论坛系统的筛选体系,快速准确地筛选鉴定疏风解毒胶囊中96种主要的化合物成分以及潜在的10种抗炎活性物质,首次明确疏风解毒胶囊的药效物质基础。进而,通过PharmMapper数据库对抗炎物质进行反向分子对接,预测出疏风解毒胶囊潜在的作用分子靶点。同时,通过构建多种LPS诱导的大鼠肺损伤的组织模型以及和炎症相关的巨噬细胞模型,结合多维蛋白质鉴定技术(MudPIT)和定量蛋白质组学技术(label-free quantification),得到疏风解毒胶囊治疗大鼠肺损伤模型后的差异蛋白表达数据。最后,通过对差异蛋白的博狗官方网站首页信息学分析,明确了AKT1在疏风解毒胶囊治疗大鼠ALI中的核心调控作用,进一步的博狗官方网站首页学实验证明多条免疫与炎症相关信号通路参与了这一调控过程。本文中对疏风解毒胶囊药理药效的分析流程为中药复方分析领域提供了全新的理念和标准,可以作为后续中药研究方法发展的标志性论文之一。 J Proteome Res:中科院生化细胞所黄超兰研究员揭示中药复方药物疏风解毒胶囊治疗急性肺损伤的
图注:疏风解毒胶囊治疗大鼠急性肺损伤的分子机制研究
原文链接: Therapeutic Mechanism Studies of ShuFengJieDu Capsule on an Acute Lung Injury Animal Model Using quantitative Proteomics Technology 原文摘要: ShuFengJieDu Capsule (SFJDC), a traditional Chinese Medicine (TCM) that comprises eight medicinal herbs, has been extensively utilized in the treatment of acute lung injury (ALI) and respiratory infections for more than 30 years in China. SFJDC has also been listed in the official guidelines of the CFDA (China Food and Drug Administration) because of its stabilized clinical manifestations. However, the underlying mechanism of SFJDC in repairing ALI remains unclear. In the present study, we explored the protective and therapeutic mechanism of SFJDC in a rat model using qualitative and quantitative proteomics. After establishing lipopolysaccharide (LPS)-induced ALI rat models, we profiled both isolated macrophage cells from freshly resected rat lung tissues from ALI models and section ALI rat lung tissues using a HPLC-MS/MS shotgun proteomics approach to identify changes in the levels of expression of proteins of interest. Based on the results of proteomics results and dysregulated protein analyses of ALI rat lung tissues and rat lung macrophages, AKT1 was selected as a putative key factor that might play an important role in the SFJDC treatment of ALI progression. Follow-up validation studies revealed that AKT1 expression effectively regulates various ALI-related molecules, and Gene Ontology analysis indicated that SFJDC-treated ALI rat macrophages were influenced by AKT1-based networks. Gain- and loss-of-function analyses via lentivirus-AKT1 or lentivirus-si-AKT1 infections into macrophages also indicated that AKT1 was essential for the development of ALI by regulating oxidative stress, apoptosis, or inflammatory responses. In summary, SFJDC effectively manipulated the biological activity in anti-inflammatory and immunomodulation activity in ALI, which might be involved in AKT1 regulation in ALI progression. New insights into SFJDC mechanisms may facilitate the development of novel pharmaceutical strategies in controlling the expression of inflammatory factors. doi:10.1021/acs.jproteome.7b00409 作者:黄超兰 点击:
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