依普利酮对高糖和IL-1β诱导的心脏成纤维细胞MMP-2表达的影响  

Effect of eplerenone on expression of MMP-2 in cardiac fibroblasts stimulated by high glucose and IL-1β

作　　者：池菊芳[1] 郭航远[1] 唐伟良[1] 吕海涛[1] 周妍[1] Hiroyasu UZUI 

机构地区：[1]绍兴市人民医院心内科,绍兴312000 [2]日本福井大学医学院附属病院

出　　处：《上海交通大学学报（医学版）》2012年第12期1571-1576,共6页Journal of Shanghai Jiao tong University:Medical Science

基　　金：浙江省自然科学基金(Y2100535);浙江省中医药科学研究基金计划(2011ZB151)~~

摘　　要：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）-113. 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-Iβ 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-1 β 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-1 [3 ＋ eplerenone group were significantly lower than those in high glucose group and normal control ＋ IL-I β 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-1 β and inhibited by eplerenone.

关 键 词：高糖 白介素1Β 基质金属蛋白酶2 盐皮质激素受体拮抗剂 成纤维细胞 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]