【摘要】 目的研究螺内酯干预肝星状细胞（HSCs）后基质金属蛋白酶2（MMP-2）、MMP-9、MMP-13和其组织抑制剂1（TIMP-1）的变化。探讨螺内酯对胶原代谢影响的机制。方法应用不同浓度螺内酯（1×10-4）mol/L^1×10-7mol/L干预HSCs 48小时,采用反转录-聚合酶链反应（RT-PCR）方法检测MMP-2、MMP-9、MMP-13 mRNA和TIMP-1 mRNA的表达。结果①螺内酯组的MMP-13基因表达强度上调,螺内酯（1×10-4）mol/L^1×10-6mol/L浓度组MMP-13基因表达强度（0.91±0.13、0.80±0.01、0.67±0.15）均明显高于对照组（0.53±0.10）（P<0.01）。1×10-4mol/L浓度组MMP-13基因表达强度接近对照组的2倍。②螺内酯干预HSCs 48小时后,TIMP-1基因表达减少,螺内酯（1×10-4）mol/L^1×10-6mol/L浓度组（0.15±0.05、0.28±0.15、0.37±0.03）明显低于对照组（0.47±0.04）（P<0.01或<0.05）。③螺内酯不同浓度干预HSCs 48小时后,HSCs MMP-2、MMP-9基因表达无明显变化（P>0.05）。结论螺内酯可抑制HSCs TIMP-1基因的表达,增加间质胶原酶MMP-13 mRNA的含量。螺内酯可能通过对MMPs及TIMP-1影响而促进胶原降解。更多还原

【Abstract】 Objective To investigate the effects of spironolactone on expression of metalloproteinases(MMP-2,MMP-9,MMP-13) and tissue inhibitor of matrix metalloproteinase-1(TIMP-1) in hepatic stellate cells(HSCs).And to study the mechanism how spironolactone affects the collagen metabolism in HSCs.Methods The activated HSCs were treated with different concentrations of spironolactone(1×10-4-1×10-7 mol/L) for 48 hours.The expressions of MMP-2,MMP-9,MMP-13 and TIMP-1 mRNA were evaluated by RT-PCR(MMPs or TIMP-1/β-actin).Results The expression of MMP-13mRNA in spironolactone groups was up-regulated.This gene expression in 1×10-4-1×10-6 mol/L spironolactone treated groups(0.91±0.13,0.80±0.01 and 0.67±0.15 respectively) was significantly higher than that in the control,0.53±0.10(P<0.01).Treatment with spironolactone for 48 hours,the expression of TIMP-1 mRNA decreased dose-dependently,and among 1×104 mol/L and 1×10-6 mol/L groups,the decrease was the most obvious(0.15±0.05,0.28±0.15 and 0.37±0.03 respectively vs control group 0.47±0.04,P<0.01 or P<0.05).MMP-2 mRNA and MMP-9 mRNA expression in HSCs stayed unchanged after incubation with different concentrations of spironolactone for 48 hours.Conclusion Spironolactone may inhibit the expression of TIMP-1 and increase MMP-13 mRNA.Spironolactone may promote the collagen degradation by regulating MMPs and TIMP-1 expression.更多还原