目的 探讨依普利酮干预对高糖和白介素1β（IL-1β）诱导的人心脏成纤维细胞基质金属蛋白酶2 (MMP-2)表达的影响。方法 将人心脏成纤维细胞分别培养在正常葡萄糖浓度（正常对照组）、高浓度葡萄糖（高糖组）和等渗甘露醇（高渗对照组）的培养液中，分别添加IL-1β和（或）盐皮质激素受体阻断剂依普利酮进行干预。明胶酶法测定细胞培养上清液中MMP-2的活性，RT-PCR测定成纤维细胞MMP-2和组织金属蛋白酶抑制因子2（TIMP-2）mRNA 的表达。结果 与正常对照组比较，高糖组MMP-2活性和mRNA的表达显著增高（P<0.01），高渗对照组MMP-2活性和mRNA表达也增高但低于高糖组（P<0.05）。与高糖组比较，高糖+IL-1β组MMP-2活性和mRNA的表达呈现叠加现象，高糖+依普利酮组和正常对照+IL-1β+依普利酮组MMP-2活性和mRNA的表达分别显著低于高糖组和正常对照+IL-1β组（P<0.05）。结论 高糖可通过高渗外的作用诱导人心脏成纤维细胞MMP-2活性增强和mRNA表达增加，IL-1β对该诱导作用具有促进作用，而依普利酮则呈现抑制效应。

Objective To investigate the effect of eplerenone on the expression of matrix metalloproteinase-2 (MMP-2) in cardiac fibroblasts stimulated by high glucose and interleukin (IL)-1β. Methods Human cardiac fibroblasts were cultured in fluid with normal glucose (normal control group), high glucose (high glucose group) and iso-osmotic mannitol (hyperosmotic control group) in the absence or presence of IL-1β and/or eplerenone. The activity of MMP-2 in the supernatant was assessed by gel zymography, and the expression of MMP-2 mRNA and tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA was determined by RT-PCR. Results The activity of MMP-2 and MMP-2 mRNA in high glucose group and hyperosmotic control group were significantly higher than those in normal control group (P<0.01, P<0.05), while the activity of MMP-2 and MMP-2 mRNA in hyperosmotic control group were significantly lower than those in high glucose group (P<0.05). There was a twofold increase in the activity of MMP-2 and expression of MMP-2 mRNA in high glucose+IL-1β group as compared with high glucose group. The activity of MMP-2 and expression of MMP-2 mRNA in high glucose+eplerenone group and normal control+IL-1β+eplerenone group were significantly lower than those in high glucose group and normal control+IL-1β group (P<0.05). Conclusion High glucose may increase the activity of MMP-2 and expression of MMP-2 mRNA in human cardiac fibroblasts through osmotic and non-osmotic pathways, which may be enhanced by IL-1β and inhibited by eplerenone.