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基于Wnt/Ca2+信号通路研究肢体缺血-再灌注损伤骨骼肌细胞凋亡机制及桃红四物汤的干预作用

基于Wnt/Ca2+信号通路研究肢体缺血-再灌注损伤骨骼肌细胞凋亡机制及桃红四物汤的干预作用
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  • 批准号:81674008
  • 批准年度: 2016年
  • 学科分类:中医骨伤科(H2710) |
  • 项目负责人:朱付平
  • 负责人职称:副教授
  • 依托单位:湖南中医药大学
  • 资助金额:59万元
  • 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: Wnt/Ca2+;缺血;再灌注损伤骨骼肌细胞凋亡;桃红四物汤;干预
  • 英文关键词:Wnt/Ca2+ signal pathway;Limb Ischemia Reperfusion Injury;Skeletal Muscle Cells Apoptosis;Taohongsiwu

项目摘要

中文摘要

肢体缺血再灌注损伤(LIRI)为严重创伤后一种常见的复杂病理过程,其病理机制尚未完全阐明,治疗缺乏特异性且疗效不确定,因而阐明其病理机制及研究有效防治具有重要意义。目前钙超载及炎症反应被公认为内脏重要器官缺血再灌注损伤的重要病理机制,而Wnt/钙离子通路在钙离子代谢及炎症反应中起着至关重要的作用,我们前期研究发现:活血化瘀类中药可以减轻LIRI骨骼肌细胞凋亡,改变钙调蛋白表达的强弱,初步揭示Wnt/钙离子通路与LIRI应有高度相关性。本项目拟在前期研究基础上,建立大鼠LIRI模型及缺氧再给氧诱导损伤的肌母细胞模型,采用流式细胞仪、激光共聚焦扫描显微系统及分子生物学等技术,通过观察Wnt/钙离子通路中基因的过表达和干扰其表达对LIRI的影响,进一步阐明其骨骼肌细胞凋亡的分子机制,并以桃红四物汤干预治疗进行反证,明确桃红四物汤治疗该病的靶点基因,为中医药治疗LIRI提供新思路和理论依据。

英文摘要

The Study on Pathogenesis of Skeletal Muscle Apoptosis in LIRI and the Intervention Effect of Taohongsiwu Decoction Based on Wnt/Ca2+ Signal Pathway. Limb ischemia reperfusion injury (LIRI) is a common complex pathological process after severe trauma. The disease pathogenesis has not yet been fully grasped, the treatment lacks of specificity, and the treatment effect is uncertain, therefore it is of great significance to clarify the pathogenesis and the effective prevention and treatment of the disease. It is generally thought that the calcium overload and the body inflammation are important mechanisms of the ischemia-reperfusion injury of vital internal organs and Wnt/Ca2+ pathway plays a very important role in calcium ion metabolism and body inflammation. Based on the previous study, we found that Chinese herbal compound prescription for activating blood circulation and removing blood stasis reduced LIRI skeletal muscle apoptosis, changed the strength of expression of calmodulin, which preliminarily presented the strong correlation between Wnt/Ca2+ pathway and LIRI. This project is planed to further demonstrate the molecular mechanism of LIRI skeletal muscle apoptosis by establishing rats LIRI model and injury muscle cell model induced by hypoxia-reoxygenation, using techniques such as flow cytometry, laser confocal scanning microscopy system, and molecular biology, and observing the gene overexpression in Wnt/Ca2+ pathway and the impact intervention effect, and besides, to identify the targeting gene of Chinese herbal compound prescription for “activating blood circulation and removing blood stasis” on it by applying Taohongsiwu decoction as an intervention treatment. In this way, we expect to provide a new thought and theoretical basis for TCM treatment of LIRI...Key words: Wnt/Ca2+ Signal Pathway;Limb Ischemia Reperfusion Injury; Skeletal Muscle Cells Apoptosis; Taohongsiwu Decoction; Study of Pathological Mechanism

评估说明

    国家自然科学基金项目“基于Wnt/Ca2+信号通路研究肢体缺血-再灌注损伤骨骼肌细胞凋亡机制及桃红四物汤的干预作用”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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