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目的:探讨地黄抗心衰作用最佳有效部位及其作用机制。方法:首先采用体外阿霉素(DOX)诱导的心肌细胞损伤模型,筛选出地黄对心肌细胞保护作用的最佳有效部位;其次采用小剂量多次腹腔注射阿霉素(DOX)诱导大鼠慢性心衰(CHF)。将最佳有效部位连续给药4周后,采用超声心动图检测大鼠左心室舒张末内径(LVEDD)和收缩末内径(LVESD)并计算左室短轴缩短率(LVFS)及射血分数(LVEF),检测大鼠血浆中BNP、c Tn I、AngⅡ、ALD和TNF-α,采用western blot检测大鼠心脏中BNP的表达。结果:地黄提取物能给药4周后,能显著改善DOX损伤心肌细胞的存活率,乙酸乙酯部位效果最佳。动物实验中模型组LVEF、LVFS、BNP、c Tn I、AngⅡ、TNF-α和心肌组织形态均有显著改变;治疗后与模型组比较,地黄乙酸乙酯各剂量组LVEF、LVFS、c Tn I、AngⅡ、ALD、TNF-α显著改善(P<0.05,P<0.01),各治疗组心肌组织病理形态不同程度好转,尤以乙酸乙酯高剂量组效果最佳。结论:地黄提取物均可提高DOX损伤心肌细胞的存活率,以乙酸乙酯部位效果最佳;乙酸乙酯高、中剂量组能明显改善CHF大鼠的心肌病理形态及血浆LVEF、LVFS、BNP、c Tn I、AngⅡ、TNF-α疾病指标。
Objective: To explore the best and effective part of Rehmannia glutinosa anti-heart failure and its mechanism. Methods: First, we used the model of cardiomyocyte injury induced by doxorubicin (DOX) in vitro and screened the best effective site of rehmannia cardiomyocyte protective effect. Secondly, Heart failure (CHF). After four weeks of continuous administration of the best effective site, left ventricular end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) were measured by echocardiography and left ventricular fractional shortening (LVFS) and ejection fraction LVEF). BNP, cTn I, AngⅡ, ALD and TNF-α were detected in plasma of rats. The expression of BNP in rat heart was detected by western blot. Results: Rehmanniae extract can significantly improve the survival rate of DOX injured cardiomyocytes after 4 weeks of administration, and the effect of ethyl acetate is the best. In the animal experiment, the LVEF, LVFS, BNP, cTn I, AngⅡ, TNF-αand the morphology of myocardial tissue in model group were significantly changed. Compared with the model group, the LVEF, LVFS, cTn I (P <0.05, P <0.01). The pathological changes of myocardium in each treatment group improved to some extent, especially in the high-dose ethyl acetate group. CONCLUSION: Rehmanniae extract can increase the survival rate of DOX-injured cardiomyocytes with the best effect of ethyl acetate. The high and middle-dose ethyl acetate groups can significantly improve the myocardial pathological morphology and plasma LVEF, LVFS, BNP , C Tn I, Ang Ⅱ, TNF-α disease index.