上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (12): 1571-.doi: 10.3969/j.issn.1674-8115.2012.12.012

• 论著（基础研究） • 上一篇    下一篇

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

池菊芳1, 郭航远1, 唐伟良1, 吕海涛1, 周 妍1, Hiroyasu UZUI2   

  1. 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, 福井 910-1193
  • 出版日期:2012-12-28 发布日期:2012-12-31
  • 通讯作者: 郭航远, 电子信箱: ghangyuan@hotmail.com。
  • 作者简介:池菊芳（1975—）, 女, 副主任医师, 硕士；电子信箱: jf_chi@163.com。
  • 基金资助:

    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）

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

CHI Ju-fang1, GUO Hang-yuan1, TANG Wei-liang1, LÜ|Hai-tao1, ZHOU Yan1, Hiroyasu UZUI2   

  1. 1.Department of Cardiology, Shaoxing People's Hospital, Shaoxing 312000, China； 2.Affiliated Hospital of Faculty of Medical Sciences, University of Fukui, Fuku 910-1193, Japan
  • Online:2012-12-28 Published:2012-12-31
  • Supported by:

    Natural Science Foundation of Zhejiang Province, Y2100535；Tradition Chinese Medicine Research Foundation of Zhejiang Province, 2011ZB151

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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。

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

Abstract:

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.

Key words: high glucose, interleukin-1β, matrix metalloproteinase-2, mineralocorticoid receptor antagonist, fibroblast