丹参单体IH764-3对肝星状细胞胶原代谢的影响及其机制研究  

Effects of salvia miltiorrhiza monomer IH764-3 on collagen metabolism and mechanism in hepatic stellate cells

作　　者：王春生[1,2] 郭金波[1] 许云峰[3] 田慧[1] 魏娟[4] 张国尊[1] 刘蕾[1] 房澍名[1] 张晓岚[1] 

机构地区：[1]河北医科大学第二医院消化科,河北省消化病重点实验室河北省消化病研究所,河北石家庄050000 [2]顺平县医院内科,河北顺平072250 [3]冀中能源峰峰集团有限公司总医院消化内科,河北邯郸056200 [4]石家庄市第五医院肝病科,河北石家庄050021

出　　处：《临床荟萃》2012年第17期1502-1505,共4页Clinical Focus

基　　金：河北省中医药管理局科研课题(2007061);河北省科技厅资助项目(09966107D)

摘　　要：目的研究丹参单体IH764-3对H2O2刺激的肝星状细胞(HSCs)胶原合成、膜型基质金属蛋白酶(MT1-MMP)、基质金属蛋白酶2(MMP-2)及其组织抑制因子(TIMP-2)表达的影响,探讨丹参单体IH764-3在调控HSCs胶原代谢中的作用机制。方法应用体外细胞培养技术,以不同剂量IH764-3干预过氧化氢(H2O2)刺激的HSCs,通过3 H-脯氨酸(3 H-Pro)掺入法检测HSCs总胶原和Ⅰ型胶原合成能力,应用Western blot技术检测MT1-MMP、MMP-2及TIMP-2蛋白的表达。结果不同剂量IH764-3(10μg/ml,20μg/ml,30μg/ml,40μg/ml)作用于H2O2刺激的HSCs 24小时,与单纯H2O2组相比,30μg/ml组和40μg/ml组能显著抑制总胶原和Ⅰ型胶原的合成(P<0.05),而H2O2组、10μg/ml组和20μg/ml组之间差异无统计学意义(P>0.05)。IH764-3干预组与H2O2组相比,能够明显上调MT1-MMP和MMP-2的表达,下调TIMP-2表达,并呈剂量依赖性关系。结论丹参单体IH764-3可能通过下调TIMP-2、上调MT1-MMP及MMP-2表达调控HSCs胶原代谢。Objective To better understand the effects of different concentrations of salvia miltiorrhiza monomer IH764-3 on collagen metabolism in hepatic stellate cells（HSCs）,the expression of membrane-type matrix metalloproteinase-1（MT1-MMP）,matrix metalloproteinase-2（MMP-2） and tissue inhibitor of metalloproteinase-2（TIMP-2） were investigated.Methods Activated HSCs were cultured in vitro prestimulated by H2O2.After treatment with different concentrations（10,20,30,40 μg/ml） of IH764-3 for 24 hours,the contents of total collagen and type Ⅰ collagen were detected by 3H-proline incorporation assay.The expression of MT1-MMP,MMP-2 and TIMP-2 were determined by western blot.Results The 30 μg/ml group and 40 μg/ml group of IH764-3 markedly inhibited total collagen and type Ⅰ collagen synthesis compared to those of the control group（P〈0.05）.There were no significant differences among the control group,10 μg/ml group and 20 μg/ml group（P〉0.05）.The IH764-3 groups（10,20,30,40 μg/ml） could up-regulate the expression of both MT1-MMP and MMP-2 and down-regulate the TIMP-2 in dose-dependent pattern.Conclusion IH764-3 can inhibit the expression of total collagen and type Ⅰ collagen in dose-dependent pattern,the mechanism may be related to the up-regulation of both MT1-MMP and MMP-2 and the down-regulation of TIMP-2.

关 键 词：肝细胞 胶原 丹参 过氧化氢 基质金属蛋白酶类 金属蛋白酶类组织抑制剂 

分 类 号：R575.2[医药卫生—消化系统]