丹酚酸A不同给药途径对犬急性心肌缺血影响

Effect of salvianolic acid A on anesthetized canine experimental myocardial infarction

丹酚酸A（salvianolic acid A,SAA）是常用中药丹参中的一种水溶性酚酸类成分,也是主要活性成分之一,研究显示具有改善心肌缺血、抗氧化、抗血栓形成等多种药理作用。然而,SAA不易通过生物膜,在胃肠道吸收时生物利用率较低。SAA静脉给药可能解决口服吸收差、起效较慢等问题。该文研究了SAA静脉注射与灌胃2种不同给药途径对犬急性心肌缺血的影响。24只犬随机分为4组,模型组、口服给药8 mg·kg-1组、静脉注射4 mg·kg-1组以及合贝爽0.5 mg·kg-1组,每组6只动物;通过结扎犬冠状动脉前降支的方法复制急性心肌缺血模型。采用心外膜电图标测心肌缺血范围及程度,定量组织学（N-BT染色法）测定心肌梗塞范围,超声多普勒血流计测定心脏冠脉血流量及心肌耗氧量,全自动生化分析仪测定血清乳酸脱氢酶（LDH）、肌酸激酶（CK）的变化。研究结果显示,丹酚酸A静脉给药及灌胃给药均明显减少NBT所示的心肌梗死/心室的比率[（13.19±2.38）%,（16.73±6.52）%,与模型组（24.35±4.89）%比较P〈0.01];口服给药明显减轻由心外膜电图标测的心肌缺血程度（∑-ST）（30~190 min,P〈0.05~0.01）,而静脉给药起效更为迅速,在缺血10 min即可见效,10~190min与模型组比较均有显著差异（P〈0.05~0.01）;口服与静脉给药均可减小由心外膜电图标测的心肌缺血范围（N-ST）;对心肌缺血及心肌梗塞引起的血清LDH,CK活性升高,2种给药途径均有明显抑制作用,但静脉给药显示出更明显的作用效果。该研究显示,SAA口服与静脉2种给药途径均表现出较好的保护心肌的作用,与口服给药比较,SAA静脉给药减轻心肌梗死作用起效时间短、作用强度更明显。

Salvianolic acid A（ SAA）,one of the major active water-soluble salvianolic acids of traditional Chinese medicine Salvia miltiorrhiza Bunge,has been reported to be effective on anti-myocardial ischemia,anti-oxidation and anti-thrombus. This study aimed to investigate appropriate administration route on dogs with acute myocardial ischemia（ AMI）. Twenty-four dogs were randomized into four groups（ n = 6）,model,oral administration of SAA（ 8 mg·kg-1）,intravenous administration of SAA（ 4 mg·kg-1）,intravenous administration of Herbesser（ 0. 5 mg·kg-1） as positive drug group. AMI model was established by ligating left anterior descending coronary arteries（ LAD） of dogs. Changes of ST segment were determined by epicardial electrocardiogram（ ECG）,coronary blood flow（ CBF） and myocardial oxygen consumption were measured by ultrasonic Doppler flow meter,serum creatine kinase（ CK） and lactate dehydrogenase（ LDH） were observed by fully automatic biochemical analyser. Myocardial infarct size was assessed by nitro blue tetrazolium（ NBT） staining. Both oral and intravenous administration of SAA reduced the myocardial infarct area / left ventricle area significantly [（ 16. 73 ± 6. 52） % and（ 13. 19 ± 2. 38） %,compared with（ 24. 35 ± 4. 89） % in model group,P〈0. 01）. Oral administration of SAA improved the ECG performance of Σ-ST from 30-190 min after ischemia（ P〈0. 05-0. 01）,while intravenous SAA had a rapid onset（ 10-190 min after ischemia,P〈0. 05-0. 01）. Compared with model group,oral and intravenous SAA both decreased serum CK and LDH significantly（ P〈0. 05-0. 01）,while the difference of intravenous administration is more significant. SAA protects myocardium in canine experimental myocardial infarction models. Intravenous administration of SAA alleviates myocardial infarction with greater significance than oral route.