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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 tannic acid (TA) sustained release microspheres on ventricular remodeling after acute myocardial infarction (AMI). Methods TA sustained-release microspheres were prepared and their in vitro drug release parameters were measured. The model of myocardial infarction in rats was established. Eighty rats were randomly divided into three groups: PLGA group (PLGA group, n = 24), PLGA-TA ) Group (n = 24), TA group (n = 16) and NS group (n = 16). Cardiac function was evaluated by echocardiography after operation. At 4 weeks after operation, myocardial extracellular matrix (ECM) was observed at the marginal tissue of myocardial infarction. Collagen content in myocardial infarction area was measured at 2 weeks and 4 weeks after operation. Results TA was continuously released from the microsphere carrier for 1 month. Left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic diameter (LVESD) were both significantly increased in PLGA-TA group and TA group (P <0.05). The LVEF, LVFS, LVEDD and LVESD of PLGA-TA group were significantly better than those of the other three groups at 4 weeks after operation (P <0.05). After 4 weeks PLGA-TA group myocardial ECM arrangement TA group more orderly and tidy. The collagen content in PLGA-TA group at 4 weeks after operation was significantly higher than that in TA group [(88.88 ± 7.28) μg / mg myocardial dry weight vs. (72.43 ± 9.02) μg / mg myocardial dry weight) (88.88 ± 7.28) μg / mg vs (.71.97 ± 6.06 μg / mg) and NS group (88.88 ± 7.28 μg / mg) and (68.86 ± 7.55 μg / mg) (F = 7.162, P = 0.003). There was no significant difference between TA group, PLGA group and NS group (P> 0.05). CONCLUSION: The intramyocardial injection of TA sustained-release microspheres can inhibit the degradation of ECM for a long time and effectively delay the occurrence of ventricular remodeling.