丹参单体IH764-3促进H_2O_2刺激的鼠肝星状细胞胶原降解

Effect of Salvia miltiorrhiza monomer IH764-3 on collagen metabolism in H_2O_2 stimulated hepatic stellate cells of rat

目的观察丹参单体IH764-3对鼠肝星状细胞株(HSCs)基质金属蛋白酶-13(MMP-13)及其组织抑制因子(TIMP-1)表达的影响。方法应用体外细胞培养技术,用RT-PCR检测HSCsMMP-13mRNA水平;原位杂交和Westernblotting技术分别检测上述细胞TIMP-1mRNA和蛋白水平。结果IH764-3干预2h组MMP-13mRNA的表达强度明显上调,同时TIMP-1mRNA表达受抑制;IH764-3干预24h组TIMP-1蛋白表达受抑制。结论丹参单体IH764-3诱导HSCsMMP-13表达,抑制其TIMP-1表达是其抗肝纤维化的作用机制之一。

Objective To investigate the effect of Salvia mfltiorrhiza monomer IH764-3 on the expression of matrix metalloproteinase-13（ MMP-13 ） and tissue inhibitor of matrix metaUoproteinases-1 （ TIMP-1 ） of hepatic steUate cells（HSCs）. Methods Expression of MMP-13 was evaluated by BT-PCR and 71MP-I was analyzed by in-situ hybridization at mRNA level and by Western blotting at protein level. Results Being incubated for 2 hrs, as compared with control group, MMP-13 mRNA was upregalated by IH764-3 but TIMP-1 transcription reduced in a dose-dependent manner. The expression of TIMP-1 protein in HSCs also decreased after exposure to IH764-3 for 24 hours. Conclusion Salvia miltiorrhiza monomer IH764-3 may upregulate MMP-13 mRNA of HSCs. And in the meantime, it can also downregulate 71MP-1 at mRNA and protein levels. This may be one of the anti-fibrotic mechanisms of Salviae miltiorrhizae.