[关键词]
[摘要]
肾间质纤维化(renal interstitial fibrosis,RIF)是肾组织损伤向终末期肾病演变的关键环节,其严重程度与临床预后直接相关。在RIF病理中,肌成纤维细胞(myofibroblast,MyoF)被认为是引发肾结构重塑和肾功能下降的核心效应细胞。慢性炎症反应以及生长因子与纤维细胞因子的异常活化能促进MyoF募集,导致肾组织中细胞外基质过度沉积。聚焦RIF中MyoF的多元起源与激活机制,探讨了肾间质成纤维细胞、周细胞、肾小管上皮细胞、内皮细胞及骨髓源性细胞向MyoF转化的条件与过程,并归纳了中药通过转化生长因子-β1(transforming growth factor-β1,TGF-β1)通路、血小板源性生长因子(platelet-derived growth factor,PDGF)通路、活性氧(reactive oxygen species,ROS)通路、刺猬信号(Hedgehog)通路等关键路径抑制MyoF激活,治疗RIF的研究进展。通过分析中药活性成分及中药复方防治RIF的具体机制及其多靶点优势,以期为中药精准治疗RIF提供更多的科学依据。
[Key word]
[Abstract]
Renal interstitial fibrosis (RIF) represents a pivotal stage in the progression of renal tissue injury to end-stage renal disease, and its severity is directly correlated with clinical prognosis. In the pathology of RIF, myofibroblasts (MyoF) are considered to be the core effector cells that trigger renal structural remodeling and the decline of renal function. Chronic inflammatory responses and abnormal activation of growth factors and fibrogenic cytokines can promote the recruitment and proliferation of MyoF, resulting in excessive extracellular matrix deposition in renal tissue. This article focuses on the multiple origins and activation mechanisms of MyoF in RIF. It investigates the conditions and transformation processes of renal interstitial fibroblasts, pericytes, renal tubular epithelial cells, endothelial cells, and bone marrow-derived cells into MyoF. Moreover, it summarizes the research progress in inhibiting the activation of MyoF and treating RIF using traditional Chinese medicine (TCM) through key pathways, such as the transforming growth factor-β1 (TGF-β1) pathway, platelet-derived growth factor pathway, reactive oxygen species (ROS) pathway, and Hedgehog signaling pathway. By analyzing the specific mechanisms and multi-target advantages of TCM active ingredients and TCM compound prescriptions in preventing and treating RIF, this article aim to provide more scientific evidence for the precise treatment of RIF with TCM.
[中图分类号]
R28
[基金项目]
国家自然科学基金资助项目(81760805);国家自然科学基金资助项目(81460682);广东省自然科学基金资助课题(2020A1515010566,2020A151501572);深圳市科技创新委员会课题项目(JCYJ20190809102413156);深圳市福田区卫生与公益事业科研专项(FTWS2022014)