基于IL-6/STAT3信号通路研究黄连提高IPA小鼠生存率的作用机制
结题报告
批准号:
82004035
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
王卓娅
依托单位:
学科分类:
中药抗病毒与感染药理
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
王卓娅
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中文摘要
侵袭性肺曲霉病(IPA)的西药治疗普遍预后不良,因而其治疗用中药的筛选与开发显得非常必要和紧迫。我们前期发现黄连可抑制烟曲霉生长,并能显著提高IPA小鼠生存率。进一步网络药理学分析表明:黄连碱、黄连素和小檗红碱和掌叶防已碱4种主要活性物质均可影响IL-6/STAT3信号通路(IS通路)多个相关基因的表达。因而我们推测,通过IS通路调节宿主免疫状态可能是黄连提高IPA小鼠生存率的重要机制。基于此,本项目拟构建细胞模型和动物模型,验证IS通路与黄连抗IPA的相关性。RNA-seq与iTRAQ联用,关联分析黄连治疗与否IPA小鼠肺组织转录组与蛋白组差异,构建免疫调节相关基因共表达网络,全方位阐明黄连基于IS通路抗IPA的分子机制。进而构建差异蛋白功能调控网络,定位IS通路调控相关核心蛋白,建立核心蛋白表达与差异基因转录相关性,筛选出IPA治疗新靶点。本项目的实施将为IPA的中药治疗研究奠定基础。
英文摘要
The screening and development of traditional Chinese medicine for the treatment of invasive pulmonary aspergillosis (IPA) is expected to improve the poor prognosis of Western medicine. In our previous studies, we have found that the decoction of Coptis chinensis can inhibit the growth rate of Aspergillus fumigatus in vitro, and improve the survival rate of mice that infected by IPA. Network pharmacology analysis showed that four main active substances, such as berberine, interact with eight core targets, including STAT3, PIK3CA and IL-6, et al. Seven of the main targets are located in the IL-6 / STAT3 signaling pathway (IS pathway). We predict that regulating host immune status through IS pathway is also the main reason for Coptis to improve the survival rate of IPA mice. Based on these evidences, we plan to build one cell model and one animal model to verify the correlation between the IS pathway and the anti-IPA ability of Coptis chinensis. Then, we will try to construct the co-expression and regulation of IS pathway related immunoregulatory genes by combination the difference analysis of lung tissue transcriptomics and proteomics of IPA mice treated with Coptis or not, and describe the molecular mechanism of Coptis chinensis to improve the survival rate of IPA mice based on the IS pathway. Furthermore, we construct the regulatory network of differential protein function, locate the core protein related to is pathway regulation, establish the correlation between the expression of core protein and differential gene transcription, and select the new target of IPA therapy. The implementation of this project will lay a foundation for the treatment study of IPA with traditional Chinese medicine.
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DOI:10.13417/j.gab.041.000454
发表时间:2022
期刊:基因组学与应用生物学
影响因子:--
作者:王卓娅;吴培诚;王艳芳
通讯作者:王艳芳
国内基金
海外基金