摘要
细胞外基质(extracellular matrixc,ECM)在肺间质的大量沉积是肺纤维化的病理特点之一。细胞转化生长因子-β1(transforming growth factor-β1,TGF-β1)与基质金属蛋白酶及其抑制因子之间存在多向调节机制,均在细胞外基质的生成与降解中发挥重要作用。中医药干预细胞外基质沉积抗肺纤维化的研究包括单药及衍生物、复方药物、成药。其中,单药及衍生物包括补气益肺类、活血通络类、养阴生津类、清热解毒类。复方药物能降低TGF-β1表达,减少ECM合成,调整基质金属蛋白酶(matrix metalloproteinases,MMPs)和组织金属蛋白酶抑制剂(tissue inhibitor of matrix metalloproteinases,TIMPs)失衡发挥作用,调控TGF-β1信号通路及基质金属蛋白酶系。目前,针对此通路的临床研究较少,且样本量小、观察周期短,可观察的相关指标亦存在局限性;动物实验研究大多集中在对TGF-β1、Smads蛋白、MMPs/TIMPs三类指标的单独检测,具体作用机制尚不明确,且Smads、MMPs、TIMPs均包括多种家族成员,众成员的功能及它们之间相互产生的作用尚待深入研究。今后,需进一步明确中药发挥抗纤维化的作用机制,为中药临床治疗肺纤维化提供新治疗靶点。
The accumulation of extracellular matrix(ECM)in the pulmonary interstitium is one of the pathological characteristics of pulmonary fibrosis.There is a multi-directional regulatory mechanism between transforming growth factor-β1(TGF-β1)and matrix metalloproteinases(MMPs)and their inhibitors,which play an important role in the formation and degradation of ECM.The present researches on Chinese medicinals intervention of ECM deposition in anti-pulmonary fibrosis include single medicine and derivatives,compound medicines and patent medicines.Among them,single medicine and derivatives include the ones for tonifying qi and benefiting the lung,or for activating blood and clearing collaterals,or for nourishing yin and generating fluid,or the ones for clearing heat and detoxifying.Compound medicines can reduce the expression of TGF-β1,and the synthesis of ECM,regulate the imbalance between MMPs and tissue inhibitor of matrix metalloproteinases(TIMPs),and regulate TGF-β1 signaling pathway and matrix metalloproteinases.At present,there are few clinical researches on this pathway,and the sample size is small,the observation period is short,and the relevant indicators that can be observed also have limitations;most of the animal experimental researches focus on the detection of TGF-β1,Smads protein,MMPs/TIMPs alone,and the specific mechanism is not clear,and Smads,MMPs,TIMPs all include a variety of family members,the function of members and the relationship between them needs further study.In the future,we need to further clarify the anti-fibrosis mechanism of Chinese medicinals,and provide a new therapeutic target for clinical treatment of pulmonary fibrosis with Chinese medicinals.
作者
张冬冬
刘晓明
李芮
ZHANG Dong-dong;LIU Xiao-ming;LI Rui(Shandong University of Traditional Chinese Medicine,Jinan,Shandong,China,250014;Shandong Provincial Hospital of Traditional Chinese Medicine,Jinan,Shandong,China,250014)
出处
《河南中医》
2021年第5期794-799,共6页
Henan Traditional Chinese Medicine
基金
山东中医药科技发展项目(2019-0088)
山东大学临床医学科技创新计划项目(202019159)。
关键词
肺纤维化
细胞外基质
基质金属蛋白酶
组织金属蛋白酶抑制剂
转化生长因子
中医药
pulmonary fibrosis
extracellular matrix
matrix metalloproteinase
tissue inhibitor of metalloproteinase
transforming growth factor
Chinese medicinals
