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黄芪甲苷缓解表柔比星相关心脏毒性的动物实验

Astragaloside Ⅳ alleviates epirubicin-induced cardiotoxicity in rats

  • 摘要:
    目的 探讨黄芪甲苷对表柔比星相关心脏毒性的心肌保护作用。
    方法 将24只Sprague-Dauley(SD)大鼠随机分为4组,分别为对照组(空白溶剂+生理盐水)、模型组(空白溶剂+表柔比星)、低剂量黄芪甲苷治疗组(15mg/kg黄芪甲苷+表柔比星)与高剂量黄芪甲苷治疗组(75mg/kg黄芪甲苷+表柔比星),每组6只。用药前及用药后2、4、6周对所有大鼠行超声心动图检查,采用两因素重复测量方差分析评估大鼠心脏收缩功能变化,评价指标包括左室射血分数(left ventricular ejection fraction, LVEF)、三尖瓣环收缩期位移(tricuspid annular plane systolic excursion, TAPSE)及右室面积变化分数(fractional area change, FAC)。用药后6周对所有大鼠心脏取材行Masson染色。
    结果 4组大鼠LVEF不存在组间、时间及组间与时间交互效应。4组大鼠TAPSE存在组间与时间交互效应(P=0.011)。随着时间延长,模型组大鼠TAPSE下降幅度较其余各组显著(P<0.05);TAPSE和FAC在4组间差异均有统计学意义(P<0.001)。模型组大鼠TAPSE和FAC在用药后2周开始下降(P<0.05);低剂量黄芪甲苷治疗组FAC在用药后4周开始下降(P<0.05);高剂量黄芪甲苷治疗组FAC在用药后6周开始下降(P<0.05)。Masson染色显示各组大鼠心肌内不同程度胶原纤维沉积,与右室收缩功能受损程度匹配。
    结论 黄芪甲苷可对抗心肌纤维化、缓解表柔比星相关的心脏毒性,高剂量疗效优于低剂量。

     

    Abstract:
    Objective To explore the cardioprotective effect of Astragaloside Ⅳ on epirubicin-related cardiotoxicity in rats.
    Methods Twenty-four Sprague-Dauley (SD) rats were randomly divided into four groups (n=6): control group (blank solvent+normal saline), model group (blank solvent+epirubicin), low-dose Astragaloside Ⅳ group (15 mg/kg Astragaloside Ⅳ+epirubicin) and high-dose Astragaloside Ⅳ group (75 mg/kg Astragaloside Ⅳ+epirubicin). All rats were examined by echocardiography before treatment and at 2, 4 and 6 weeks after treatment. Left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC) were recorded and evaluated by two-factor repeated measures analysis of variance. The cardiac tissue slices were collected for Masson staining at 6 week after treatment.
    Results There was no significant group effect, time effect and interaction effect in LVEF. There was interaction effect in TAPSE (P=0.011). With the extension of time, the decrease of TAPSE in the model group was more significant than that in other groups (P < 0.05). TAPSE and FAC were significantly different among the four groups (P < 0.001). Compared with the control group, TAPSE and FAC in the model group decreased significantly at 2 week after treatment, and the FAC in the low-dose and high-dose Astragaloside Ⅳ group decreased significantly at 4 and 6 week after treatment, respectively. Masson staining showed that different degrees of collagen fiber deposition in the myocardium, matching the right ventricular systolic dysfunction according to echocardiography.
    Conclusion Astragaloside Ⅳ can improve epirubicin-induced cardiotoxicity by alleviating myocardial fibrosis, and the effect of the high-dose is better than the low-dose.

     

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