脑钠肽静脉滴注抑制大鼠心肌梗死后的心室重构  

Long-term infusion of brain natriuretic peptide suppresses post myocardial infarction ventricular remodeling in rats

作　　者：潘晔生[1] 魏盟[1] 朱伟[1] 马健[1] 辛平[1] 徐振兴[1] 韩蓓蓓[1] 何亚萍[1] 

机构地区：[1]上海交通大学附属第六人民医院心内科,上海200233

出　　处：《中华老年多器官疾病杂志》2011年第5期443-449,共7页Chinese Journal of Multiple Organ Diseases in the Elderly

摘　　要：目的验证和比较持续静脉滴注外源性脑钠肽(BNP)和依那普利灌胃对于心肌梗死后心室重构的抑制作用,并观察其对心肌基质金属蛋白酶(MMPs)的影响。方法 SD大鼠随机分为4组:假手术组;对照组;心肌梗死+依那普利[10mg/(kg·d)]灌胃治疗组;心肌梗死+脑钠肽[0.06μg/(kg·min)]持续静脉微泵推注治疗组。应用超声心动图、免疫组化、ELISA和Western blot等方法评估各组的心室重构和心功能状况。结果 BNP和依那普利可抑制大鼠心肌梗死后左室质量指数的增加(分别减少13.2%和16.9%,P<0.05),改善心肌梗死后大鼠的左室舒张未压(分别降低33.0%和45.8%,P<0.05)。超声心动图结果提示,给予BNP和依那普利持续治疗28天后,其左室舒张末径(LVEDD)大小和左室短轴收缩率(FS)优于对照组[LVEDD:对照组(8.8±0.6)mm,依那普利组(7.5±0.7)mm,脑钠肽组(7.5±1.0)mm,P<0.05;FS:对照组(19.2±2.6)%,依那普利组(27.7±5.6)%,脑钠肽组(27.5±3.9)%,P<0.05]。依那普利和BNP都能够明显抑制心肌梗死后期非梗死区的胶原、特别是Ⅰ型胶原的增生[对照组(6.8±1.4)%,依那普利组(4.0±0.9)%,脑钠肽组(3.7±1.1)%;P<0.05]。静脉输注BNP治疗可升高心肌的cGMP含量,但抑制心肌血管紧张素Ⅱ的作用不及依那普利。BNP对非梗死区MMP-2和MMP-9含量无明月显影响。结论心肌梗死后持续静脉给予BNP可能通过cGMP介导的信号途径发挥其心脏保护作用,包括抑制心肌梗死后的心脏肥厚、心室扩大,改善心功能,减少非梗死区心肌胶原沉积,对非梗死区MMP-2和MMP-9的表达并无明显影响。Objective To compare protective effects of chronic brain natriuretic peptide（BNP） infusion and enalapril administration on post myocardial infarction（MI） ventricular remodeling,and to investigate their effects on the matrix metalloproteinase（MMPs） expression in myocardium.Methods Rats were randomly assigned to sham-operated group,MI group in which MI models were prepared by coronary ligation,BNP group in which MI rats received chronic BNP infusion[0.06μg/（kg·min）] and enalapril group in which MI rats received enalapril administration[10mg/（kg·d）].Ventricular remodeling and heart function were estimated by echocardiography（ECG）,immunohistochemistry,ELISA and Western blot.Results Exogenous BNP infusion maintained a higher BNP level in heart tissue.BNP treatment achieved similar protective effects as enalapril therapy on postinfarction myocardial remodeling.Both BNP and enalapril inhibited the increase of left ventricular weight index by 13.2%and 16.9% respectively,（P0.05）,decreased left ventricle end pressure by 33.0%and 45.8%respectively（P0.05）.ECG results demonstrated that left ventricular end-diastolic diameter（LVEDD） and fractional shortening（FS） were more satisfactory in BNP and enalapril groups than in MI group[LVEDD：（8.8±0.6）mm in MI group,（7.5±0.7）mm in enalapril group,and（7.5±1.0） mm in BNP group, P0.05;FS：（19.2±2.6）%in MI group,（27.7±5.6）%in enalapril group,and（27.5±3.9）%in BNP group,P0.05].Both enalapril and BNP inhibited collagen deposition in non-infarcted area obviously,especially typeⅠcollegen,by（6.8＋1.4）%in MI group, （4.0±0.9）%in enalapril group,and（3.7±1.1）%in BNP group respectively（P0.05）.BNP infusion increased cyclic guanosine monophosphate（cGMP） concentration in cardiac tissue more significantly than enalapril,while inhibited angiotensin IF less significantly than enalapril.BNP infusion did not lead to obvious change of MMP-2 and MMP-9 content in non-infarcted area. Conclusion Continuous BNP in

关 键 词：心肌梗死 心室重构 利钠肽 脑 

分 类 号：R322.11[医药卫生—人体解剖和组织胚胎学]