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巨噬细胞极化通过调控PSC活化对慢性胰腺炎胰腺纤维化的影响及大柴胡汤对其干预机制研究

巨噬细胞极化通过调控PSC活化对慢性胰腺炎胰腺纤维化的影响及大柴胡汤对其干预机制研究
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  • 批准号:81673816
  • 批准年度: 2016年
  • 学科分类:中西医结合临床基础(H2902) |
  • 项目负责人:张红
  • 负责人职称:教授
  • 依托单位:陕西中医药大学
  • 资助金额:52万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: 巨噬细胞;PSC;慢性胰腺炎;胰腺纤维化;大柴胡汤
  • 英文关键词:chronic pancreatitis;pancreatic stellate cell ;macrophage polarization;Dachaihu Decoction;the molecu

项目摘要

中文摘要

胰腺星状细胞(PSC)活化是慢性胰腺炎(CP)胰腺纤维化的核心事件,近来的研究发现,PSC活化的同时伴随胰腺大量巨噬细胞(Mφ)浸润。最新研究表明:Mφ在CP进展中发生了极化偏移,且与胰腺纤维化相关,但是极化的Mφ对胰腺纤维化的确切影响和调控机制尚不清楚。拟采用Dil标记的不同极化状态Mφ尾静脉注射回输至SCID小鼠体内,及Mφ-PSC非接触性共培养体系,结合流式细胞、Luminex等技术,研究不同极化状态Mφ对PSC活化的调控作用,及对胰腺纤维化的影响,明确致PSC活化的“Mφ主凶”,阐明“通过调控Mφ极化稳态改善胰腺纤维化”的理论,为CP防治提供全新策略。大柴胡汤治疗CP疗效确切,但抗胰腺纤维化的机制不清。拟通过在体和离体实验,研究大柴胡汤是否通过调控Mφ的极化稳态,进而减轻PSC活化、抑制胰腺纤维化,阐明大柴胡汤防治胰腺纤维化的分子机制,为其在CP的临床应用提供实验依据。

英文摘要

Activation of pancreatic stellate cells (PSC) is the central event of the pancreatic fibrosis in chronic pancreatitis (CP). In recent years, the studies found PSC activation accompanied large numbers of macrophages (Mφ) infiltration in pancreatic tissue during the development of CP. What is the role of these macrophages in PSC activation and pancreatic fibrosis?The latest research shows that macrophage polarization can be seen in the pancreatic fibrosis. The numbers of M2 macrophages is proportional to pancreatic fibrosis, but the influence and mechanism of macrophages polarization on pancreatic fibrosis is not known. We intend to transfuse the different polarization of macrophage(M1 macrophage and M2 macrophage) labeled with DIL to SCID mice from tail vein directly and use the co-culture system of macrophages and PSC, as well as the techniques of flow cytometry and Luminex to explore the role of macrophage polarization in the activation of PSC and pancreatic fibrosis, to search the key targets induced PSC activation. We hope to verify the theory that the regulation of macrophage polarization is a measure to improve pancreatic fibrosis and provide a new strategy for the prevention and treatment of CP. .Furthermore, Dachaihu Decoction is a classic prescription for restraining inflammatory response. The effect of Dachaihu Decoction on pancreatic fibrosis is confirmed, but its mechanism is unclear. By vivo and vitro experiments, we intend to research whether Dachaihu Decoction regulate the polarization of macrophages or promote polarized macrophages transformed well, thereby reducing PSC activation and inhibiting pancreatic fibrosis. We hope to elucidate the molecular mechanism of Dachaihu Decoction treating pancreatic fibrosis, and provide the support for clinical application of Dachaihu Decoction in CP.

评估说明

    国家自然科学基金项目“巨噬细胞极化通过调控PSC活化对慢性胰腺炎胰腺纤维化的影响及大柴胡汤对其干预机制研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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