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[摘要]
目的 研究毛郁金醋酸乙酯提取物(CAEE)对大鼠心肌缺血再灌注损伤的治疗作用。方法 采用大鼠冠脉前降支结扎释放制备心肌缺血再灌注损伤模型,造模成功大鼠随机分为7组,即模型组,CAEE (生药)0.5、1、2、4 g/kg组,地奥心血康组,单硝酸异山梨酯组,每组10只,另设假手术组10只。各组连续治疗给药7 d。测定各组大鼠心肌梗死范围及心脏功能、心脏构型指标,测定血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)活性,测定血清氧化应激因子超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)、丙二醛(MDA)水平,观察心肌组织病理学变化。结果 与模型组相比,CAEE 1、2、4 g/kg组减小心肌梗死范围、增加射血分数(EF);CAEE 2、4 g/kg增加左室内压最大上升速率(+LVdp/dtmax),CAEE 4 g/kg增加左室内压最大下降速率(−LVdp/dtmax);CAEE可不同程度降低CK-MB、LDH心肌酶水平;可调节氧化/抗氧化平衡,提高SOD/MDA、GSH/MDA值,并使心肌细胞肿胀和炎性细胞浸润减轻。结论 CAEE对心肌缺血再灌注损伤具有治疗作用,其机制可能与调节氧化/抗氧化平衡有关。
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[Abstract]
Objective To investigate the effect of Curcuma aromatica ethylacetate extracts (CAEE) on myocardial ischemia reperfusion injury in rats.Methods The myocardial ischemia-reperfusion (I/R) injury model was established by the ligation and release of descending coronary artery in rats. I/R rats were equally divided into seven groups (i.e model group, four CAEE groups with 0.5, 1, 2, and 4 g/kg, two positive control groups with Di'ao Capsule or isosorbide mononitrate) with 10 rats in each group. In addition, 10 rats without I/R were arranged as Sham group. Each group was treated with corresponding drugs once daily for 7 d. The myocardial infarction area, cardiac function and cardiac geometric alteration were measured. Serum LDH and CK-MB were measured by chemical method and enzyme linked immunosorbent assays. The oxidative stress cytokines involving serum SOD, MDA, and GSH were measured by chemical methods. The myocardial tissue lesion was observed by histopathology.Results Compared with model group, myocardial infarction area was decreased in CAEE group with 1, 2, and 4 g/kg (crude drug), and the ejection fraction (EF) and the left ventricular pressure maximum rise/fall rates (±LVdp/dtmax) were increased in different degree treated with CAEE. Serum CK-MB and LDH were decreased in CAEE group. The oxidation/anti-oxidation balance can be adjusted by CAEE administration, the ratios of serum SOD/MDA and GSH/MDA were increased accompanying with trend increasing of SOD and GSH. The light microscopic myocardial tissue edema levels and inflammatory cell infiltration were significantly lightened in the CAEE group than the model group.Conclusion CAEE showed therapeutic benefits on rats in myocardial ischemia-reperfusion injury via the potential mechanism of balance status of oxidation and anti-oxidation.
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[基金项目]
重大新药创制资助项目(2017ZX09301046)