基础医学与临床 ›› 2010, Vol. 30 ›› Issue (11): 1177-1183.

• 研究论文 • 上一篇    下一篇

β3肾上腺素能受体激动剂和抑制剂对心衰大鼠心室MMP2和9表达的影响

孔一慧 曹荣元 张莉 刘玉冰 李悦 李为民   

  1. 哈尔滨医科大学附属第一医院
  • 收稿日期:2009-11-26 修回日期:2010-03-01 出版日期:2010-11-05 发布日期:2010-11-05

Effect of β3 adrenergic receptor agonist and antagonist on expression of MMP-2 and MMP-9 in heart failure rat

Yi-hui KONG, Rong-yuan CAO, Li ZHANG, Yu-bing LIU, Yue LI, Wei-min LI   

  1. The First Affiliated Hospital of Harbin Medical University
  • Received:2009-11-26 Revised:2010-03-01 Online:2010-11-05 Published:2010-11-05

摘要: 目的 研究β3肾上腺素能受体(AR)激动剂和抑制剂对心衰(HF)大鼠左室基质金属蛋白酶2、9(MMP-2、MMP-9)表达的影响,明确β3AR在左室重构中的作用。方法 Wistar大鼠140只,随机分为对照组10只,余130只制备HF模型,选取心衰大鼠随机分为HF组(n=11)、激动剂组(n=12)、抑制剂组(n=10)。激动剂组、抑制剂组分别给予BRL37344 1.65?g/kg、SR59230A 50?g/kg尾静脉注射,2次/周。分别于4和8周时各组选取5只大鼠测定以下指标:心功能的相关指标、左室重量/体质量、心肌胶原容积分数、MMP-2、MMP-9蛋白和mRNA表达。结果 与对照组比较,HF组大鼠心功能明显下降,激动剂组随时间增加心功能恶化较HF组更明显,而抑制剂组心功能明显改善;与对照组比较,HF组MMP-2、MMP-9 mRNA、蛋白表达增高;激动剂组增加更明显; 拮抗剂组表达减少(均为P<0.01)。结论 β3AR抑制剂改善心功能可能通过抑制心肌MMP-2、MMP-9表达来实现。

关键词: 心力衰竭, 充血性, 左室重构, 受体, 肾上腺素能β3, 基质金属蛋白酶

Abstract: Objective To investigate the effect of β3 adrenergic receptor (AR)agonist and antagonist on matrix metalloproteinases(MMP)-2 and MMP-9 in heart failure rat model and to study the relations betweenβ3AR and left ventricular remodeling. Methods Ten rats served as control group and 130 rats received isoproterenol to make heart failure model. Heart failure rats were randomly divided into agonist group(n=12), antagonist group(n=10), heart failure group(n=11). Agonist group and antagonist group received BRL37344 1.65μg/kg、SR59230A 50μg/kg through caudal vein for 10 min twice a week dividually. All below were measured at the 4th and 8th week: cardiac function, ratio of LV weight and body weigh(LVW/BW) and collagen volume fraction(CVF), expression of MMP-2 and MMP-9 proteins by the techniques of immuno-histochemistry; the expression levels of MMP-2 and MMP-9 mRNA in myocardium by reverse transcription-polymerase chain reaction (RT-PCR).Results Compared with control group,the cardiac function of heart failure group was aggravated while the cardiac function of agonist group was further aggravated; These change were significantly attenuated in antagonist group; In comparison with the control group, The expressions of MMP-2 and MMP-9 mRNA and proteins increased with time in heart failure models, and SR59230A treatment decreased the expression(all P<0.01). Conclusions β3AR may play a role in left ventricular remodeling by the effect of MMP-2 and MMP-9.