单宁酸缓释微球延缓大鼠心室重构的实验研究  

Slow Release Microspheres of Tannic Acid Attenuate Postinfarction Remodeling in Rats

作　　者：李兵[1,2] 官宝礼[1,2] 郑建华 孟健[1] 刘立群[2] 王士忠[2] 张浩[1] 

机构地区：[1]中国医学科学院北京协和医学院国家心血管病中心阜外心血管病医院心血管疾病国家重点实验室,北京100037 [2]潍坊医学院附属医院心胸血管外科,山东潍坊261031 [3]北京中海康医药科技发展有限公司,北京100082

出　　处：《中国胸心血管外科临床杂志》2012年第6期648-653,共6页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：霍英东教育基金会高等院校青年教师基金资助项目(121041)~~

摘　　要：目的探讨单宁酸(tannic acid,TA)缓释微球心肌注射对急性心肌梗死(acute myocardial infarction,AMI)后心室重构的影响。方法制备TA缓释微球,检测其体外释放药物参数。制备大鼠心肌梗死模型,将80只大鼠按随机数字表法分为空白微球组[聚乳酸-羟基乙酸共聚物(PLGA)组,n=24]、TA缓释微球(PLGA-TA)组(n=24)、TA组(n=16)和生理盐水(NS)组(n=16)。术后用超声心动图评价心功能;术后4周,观察心肌梗死边缘组织的心肌细胞外基质(ECM)排列;术后2周和4周,测定心肌梗死区胶原蛋白含量。结果 TA持续从微球载体中释放1个月。术后2周PLGA-TA组、TA组的左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、左心室舒张期末内径(LVEDD)和左心室收缩期末内径(LVESD)指标均明显优于其它两组(P<0.05);术后4周,PLGA-TA组的LVEF、LVFS、LVEDD、LVESD指标均明显优于其它3组(P<0.05)。术后4周PLGA-TA组心肌ECM排列较TA组更为有序整齐。术后4周PLGA-TA组的心肌梗死区胶原蛋白含量高于TA组[(88.88±7.28)μg/mg心肌干重vs.(72.43±9.02)μg/mg心肌干重]、PLGA组[(88.88±7.28)μg/mg心肌干重vs(.71.97±6.06)μg/mg心肌干重]和NS组[(88.88±7.28)μg/mg心肌干重vs.(68.86±7.55)μg/mg心肌干重],差异有统计学意义(F=7.162,P=0.003);而TA组、PLGA组、NS组之间比较差异无统计学意义(P>0.05)。结论 TA缓释微球心肌注射可较长时间遏制AMI后ECM的降解,有效延缓心室重构的发生。Objective To investigate the effect of intramyocardial injection of slow release microspheres of tannic acid（TA） on ventricular remodeling after acute myocardial infarction（AMI） in rats.Methods Slow release microspheres of TA were prepared and the release parameters in vitro were detected.AMI model in rats was induced.Eighty rats were enrolled and divided into 4 groups by random digital table：poly（lactic-co-glycolic acid）（PLGA） microspheres injection（PLGA group,n=24）,PLGA-TA microspheres injection（PLGA-TA group,n=24）,TA injection group（TA group,n=16） and normal saline injection group（NS group,n=16）.Heart function was evaluated by echocardiography after the injection.The structure of cardiac extracellular matrix（ECM） in the infarcted borderline area was evaluated at 4th week after the injection.Collagen content in the infarcted area was evaluated by hydroxyproline colorimetry assay at 2nd and 4th week after the injection.Results TA release was maintained at a constant rate from the microspheres for one month in vitro.Two weeks after the injection,left ventricular ejection fraction（LVEF）,left ventricular fraction shortening（LVFS）,left ventricular end-diastolic diameter（LVEDD） and left ventricular end-systolic diameter（LVESD） in PLGA-TA group and TA group were significantly better than those in the other two groups（P0.05）.Four weeks after the injection,LVEF,LVFS,LVEDD and LVESD in PLGA-TA group were significantly better than those in the other three groups（P0.05）.Four weeks after the injection,slow release microspheres of TA in the PLGA-TA group effectively improved the arrangement of ECM compared with TA group.Four weeks after the injection,collagen content in the infarcted area of PLGA-TA group was significantly higher than that in TA group（88.88±7.28 μg/mg dry weight vs.72.43±9.02 μg/mg dry weight）,PLGA group（88.88±7.28 μg/mg drg weight vs.71.97±6.06 μg/mg dry weight） and NS group（88.88±7.28 μg/mg dry weight vs.68.86±7.55 μg/mg dr

关 键 词：心肌梗死 心室重构 单宁酸 药物缓释 心肌注射 

分 类 号：R542.22[医药卫生—心血管疾病]