温阳化积法调控NETs介导补体活化干预膜性肾病足细胞损伤机制研究
批准号:
81973793
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
刘宝利
依托单位:
学科分类:
中医内科学
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
刘宝利
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中文摘要
补体活化诱导C5b-9攻膜复合物形成致足细胞损伤是膜性肾病(MN)的主要发病机制。我们及同行研究表明:炎症环境下中性粒细胞胞外陷阱网(NETs)生成同时可暴露PLA2R1抗原诱发自身免疫反应;而NETs也可直接或通过活化补体间接损伤足细胞。团队经多年临床实践认为:膜性肾病阴证居多,外寒内虚、癥积形成是其核心病机。课题组从温阳化积法入手,发现麻黄附子汤合肾着汤临床治疗MN可显著减少蛋白尿,提高血浆白蛋白水平。因此,我们提出假说,该方可能通过抑制NETs形成,从而减少PLA2R1抗原暴露及减轻补体活化,缓解肾损伤。本课题拟采用上方干预被动型Heymann肾炎大鼠及体外足细胞损伤模型,分别对相关标本的MPO等NETs组分、C5b-9等补体成分以及Nephrin、Podocin等足细胞标志蛋白进行检测,在探究MN发病机制的基础上,进而挖掘该方案治疗MN的有效靶点,为推广中医药治疗MN提供实验证据。
英文摘要
Complement activation induces membrane attack complex, namely C5b-9, injury podocytes, which is the main pathogenesis of membranous nephropathy (MN). Our and peer studies have shown that the neutrophil extracellular traps (NETs) is produced, and that it can expose PLA2R1 as an antigen, leading to autoimmune response, and activating complement to participate in pathogenesis in an inflammatory environment. NETs can also directly or indirectly by activating complement injury podocytes. After years of clinical practice, our team believes that membranous nephropathy has Yin syndrome in the majority, andexogenous cold and interior deficiency induces the formation of Zheng-Ji is its core pathogenesis. Our research group started from the method of Wenyang Huaji and found that Mahuang-Fuzi decoction and Shenzhuo decoction can significantly reduce proteinuria and improve the level of plasma albumin in the clinical treatment of MN. Therefore, we hypothesized that this decoction may reduce the explosure of antigen activation of complement by inhibiting NETs formation, thereby alleviating renal injury. In our study, this decoction would be proposed to intervene in the model of passive Heymann nephritis in rats and in vitro injury model in podocytes. We would detect the NETs components of related specimens such as MPO, c5b-9 and other complement components, as well as the marker proteins of podocytes such as Nephrin and Podocin and others. Then, on the basis of exploring the mechanism of MN, the effective target of this decoction for MN treatment would be explored to provide experimental evidence for TCM treatment of MN.
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专利列表
Idiopathic Membranous Nephropathy: Glomerular Pathological Pattern Caused by Extrarenal Immunity Activity.
特发性膜性肾病:肾外免疫活性引起的肾小球病理模式
DOI:10.3389/fimmu.2020.01846
发表时间:2020
期刊:Frontiers in immunology
影响因子:7.3
作者:Liu W;Gao C;Liu Z;Dai H;Feng Z;Dong Z;Zheng Y;Gao Y;Tian X;Liu B
通讯作者:Liu B
DOI:10.3389/fphar.2022.820130
发表时间:2022
期刊:FRONTIERS IN PHARMACOLOGY
影响因子:5.6
作者:Gao, Yu;Dai, Haoran;Zhang, Na;Jiang, Hanxue;Zhang, Zihan;Feng, Zhendong;Dong, Zhaocheng;Liu, Wenbin;Liu, Fei;Dong, Xuan;Zhao, Qihan;Zhou, Xiaoshan;Du, Jieli;Zhang, Naiqian;Rui, Hongliang;Liu, Baoli
通讯作者:Liu, Baoli
Helper T Cells in Idiopathic Membranous Nephropathy.
特发性膜肾病中的辅助T细胞。
DOI:10.3389/fimmu.2021.665629
发表时间:2021
期刊:Frontiers in immunology
影响因子:7.3
作者:Zhao Q;Dai H;Liu X;Jiang H;Liu W;Feng Z;Zhang N;Gao Y;Dong Z;Zhou X;Du J;Zhang N;Rui H;Yuan L;Liu B
通讯作者:Liu B
DOI:10.3892/etm.2021.10169
发表时间:2021-07
期刊:Experimental and therapeutic medicine
影响因子:2.7
作者:Dong Z;Dai H;Gao Y;Feng Z;Liu W;Liu F;Zhang Z;Ma F;Xie X;Zhu Z;Liu W;Liu B
通讯作者:Liu B
DOI:10.3389/fimmu.2022.926368
发表时间:2022
期刊:Frontiers in immunology
影响因子:7.3
作者:
通讯作者:
从IL-35/pSTAT3/Blimp-1通路介导Breg细胞调控生发中心反应探讨温阳解表法治疗膜性肾病机制
- 批准号:82374368
- 项目类别:面上项目
- 资助金额:51万元
- 批准年份:2023
- 负责人:刘宝利
- 依托单位:
基于Wnt/STAT3/HIF-1α调控CD4+T细胞代谢重编程探讨温阳解表法重塑膜性肾病Th/Treg细胞免疫平衡机制
- 批准号:--
- 项目类别:面上项目
- 资助金额:55万元
- 批准年份:2021
- 负责人:刘宝利
- 依托单位:
基于Wnt/β-catenin信号通路探讨从少阴太阴合方干预PHN足细胞损伤机制研究
- 批准号:81673907
- 项目类别:面上项目
- 资助金额:59.0万元
- 批准年份:2016
- 负责人:刘宝利
- 依托单位:
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