β_3肾上腺素能受体激动剂和抑制剂对心衰大鼠心室MMP-2和MMP-9表达的影响  

Effect of β_3 adrenergic receptor agonist and antagonist on expression of MMP-2 and MMP-9 in heart failure rat

作　　者：孔一慧[1] 曹荣元[1] 张莉[1] 刘玉冰[1] 李悦[1] 李为民[1] 

机构地区：[1]哈尔滨医科大学附属第一医院心内科,黑龙江哈尔滨150001

出　　处：《基础医学与临床》2010年第11期1177-1183,共7页Basic and Clinical Medicine

基　　金：黑龙江省教育厅项目(11531108);哈尔滨医科大学研究生创新基金

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)和抑制剂组(n=10)。激动剂组和抑制剂组分别给予BRL37344 1.65μg/kg、SR59230A 50μg/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、左室质量/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-9mRNA、蛋白表达增高;激动剂组增加更明显;拮抗剂组表达减少(均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。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 potential relationship between β3 AR 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） and heart failure group（n=11）.Agonist group and antagonist group received BRL37344 1.65 μg/kg or SR59230A 50 μg/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 were examined by reverse transcription-polymerase chain reaction（RT-PCR）.Results Compared with control group,the cardiac function of heart failure group wasaggravated 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 P0.01）.Conclusion β3AR may play a role in left ventricular remodeling by the effect of MMP-2 and MMP-9.

关 键 词：心力衰竭 左室重构 Β3肾上腺素能受体 基质金属蛋白酶 

分 类 号：R541.6[医药卫生—心血管疾病]