丹酚酸B在体外对基质金属蛋白酶1、2和9活性的抑制作用(英文)  

Salvianolic acid B in vitro inhibited matrix metalloproteinases-1,-2, and -9 activities

作　　者：梁雅慧[1] 李萍[2] 黄启福[1] 赵京霞[2] 刘欣[2] 戴淼可[2] 

机构地区：[1]北京中医药大学基础医学院病理学教研室,北京100029 [2]北京市中医研究所病理生理室,北京100010

出　　处：《中西医结合学报》2009年第2期145-150,共6页Journal of Chinese Integrative Medicine

基　　金：北京市自然科学基金资助项目(No.7072014)

摘　　要：目的:基质金属蛋白酶家族(matrix metalloproteinases,MMPs)是一类活性依赖于金属锌离子的蛋白酶,它可以降解绝大多数细胞外基质成分。MMPs水解蛋白质的特性有利于创伤愈合过程中坏死组织的清除,以及细胞的迁移。降低慢性创面升高的MMPs活性可能是治疗慢性皮肤溃疡的新途径。丹参外用可治疗慢性皮肤溃疡,丹酚酸B(salvianolic acid B,SalB)是丹参中含量丰富且具有较高生物活性的水溶性成分。本研究主要观察SalB在体外对MMPs的活性是否有直接影响。方法:人MMP-1和MMP-2被醋酸氨基苯汞(p-aminophenylmercuric acetate,APMA)激活后,与不同浓度的SalB共同孵育1h,通过底物裂解法观察其活性的改变。MMP-9在中性粒细胞(polymorphonuclear neutrophil,PMN)中含量丰富,因此以大鼠腹腔PMN作为MMP-9的来源。PMN裂解产物与不同浓度的Sal B共同孵育1h,通过明胶酶谱法,观察其中MMP-9活性的改变。结果:Sal B在0.0024～0.3g/L浓度范围内对MMP-1和MMP-2的活性有抑制作用,半抑制浓度(50% inhibiting concentration,IC50)分别为(0.090±0.015)g/L和(0.080±0.005)g/L;在0.003～0.3g/L浓度范围内对MMP-9的活性表现出不同程度的抑制作用(P<0.01),其抑制作用呈浓度依赖性。结论:SalB可抑制MMPs的活性,改善慢性创面高酶活性是丹参治疗慢性皮肤溃疡的作用机制之一。Objective： Matrix metalloproteinases （MMPs） are a family of zinc-dependent endopeptidases, which as a group can degrade essentially all extracellular matrix components. The proteolytic property of the MMPs is important during wound healing to remove debris and facilitate cell migration. Targeting towards the decreased MMPs activities is a new treatment strategy for healing chronic wounds. Salvia miltiorrhiza is a popular Chinese herb that could promote chronic ulcers healing for topical use. Salvianolic acid B （Sal B） is the most abundant bioactive component in Salvia miltiorrhiza. The research was designed to explore the inhibitory effects of Sal B on MMP-1, MMP-2 and MMP-9 activities. Methods： Pure human interstitial collagenase （MMP-1） or gelatinase A （MMP-2） was activated by p-aminophenylmercuric acetate （APMA）, and was incubated with Sal B for 1 h. The activities were observed by quenched fluorescent substrate. Gelatinase B （MMP-9） is rich in polymorphonuclear neutrophils （PMN）, so the rat PMN was used as a source of MMP-9 for MMPs activity assays. In vitro MMP-9 from rats PMN lysate was incubated with Sal B for 1 h, and its activity was tested by gelatin zymography. Results： Sal B dose-dependently inhibited the human MMP-1 and MMP-2 activities in the range of 0.002 ,1 to 0.3 g/L, with 50% inhibiting concentration （IC50） of （0. 090±0. 015） g/L and （0. 080±0. 005） g/L respectively. In the range of 0.003 to 0.3 g/L, Sal Bcould inhibit the MMP-9 activity （P〈0.01）. Conclusion ： The broad-spectrum inhibitory effects of Sal B on MMPs may reveal one of the mechanisms for the effects of Salvia rniltiorrhiza on chronic wounds.

关 键 词：丹参 丹参酚 基质金属蛋白酶类 大鼠 

分 类 号：R285.5[医药卫生—中药学]