大株红景天注射液对慢性心力衰竭大鼠心功能的影响及其机制研究

    Effects and mechanism of Sofren Injection on cardiac function in rats with chronic heart failure

    • 摘要:
      目的 探讨大株红景天注射液对慢性心力衰竭(chronic heart failure, CHF)大鼠心功能及肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system, RASS)的影响。
      方法 腹腔注射阿霉素法制备心力衰竭大鼠模型,选择75只SD雄性大鼠,随机选择15只作为空白对照组,60只经腹膜内给予阿霉素(4 µg/g),6周后,所有动物LVEF<60%。将实验组大鼠随机分成模型对照组、大株红景天注射液高、中、低剂量组。每天尾静脉注入6、4 和2 ml/kg的红景天注射液一次,连续2周。空白对照组和模型对照组均接受生理盐水。2周末评估各组大鼠超声心动图指数,检测血清脑钠肽(brain natriuretic peptide,BNP)、RASS相关指数,并观察心肌组织形态。从外周血中提取miRNA423-5p、miRNA499-5p和miRNA210-3p,对比其在红景天注射液组大鼠与空白对照组大鼠表达量。
      结果 不同剂量组大株红景天注射液均降低了左室舒张末内径(LVEDV)和左室收缩末内径(LVESV),同时增加了左室射血分数(LVEF)和左室短轴缩短率(LVFS),且呈现剂量依赖性。大株红景天注射液可降低心力衰竭模型大鼠的血浆miR-210-3p、miR-423-5p、miRNA-499表达水平、BNP水平以及心力衰竭大鼠的RASS指数(P<0.05)。
      结论 大株红景天注射液有抑制RASS过度激活的作用,可改善心功能,miR-423-5P、miRNA-499和miR-210-3P可作为CHF的血清生物标记物。

       

      Abstract:
      AIM To investigate the effect of Sofren Injection on myocardial cell morphology, cardiac function and ventricular remodeling in rats with heart failure.
      METHODS Seventy-five SD male rats were selected, of whom 15 were randomly selected as a blank control group and 60 were treated intraperitoneally with doxorubicin (4 μg/g). After 6 weeks, LVEF was <60% in all animals. A heart failure model was established. The experiment group was divided into model control, low-dose, medium-dose, and high-dose Sofren Injection groups, with 15 rats in each group. 2ml/kg of Sofren Injection was injected into the tail vein once a day for 2 weeks and blank control group received normal daily saline. After 2 weeks, the echocardiographic index, RASS-related index and serum BNP level were assessed in all rats, and myocardial tissue morphology was observed. miRNA423-5p, miRNA499-5p, and miRNA210-3p were extracted from peripheral blood and their expressions were examined and compared with those of the healthy control rats.
      RESULTS 6 ml/kg Sofren Injection lowered LVEDV and LVESV while increasing LVEF and LVFS. Injections of 6 ml/kg Rhodiolarosea reduced plasma levels of miR-210-3p, miR-423- 5p, miRNA-499 and BNP in heart failure model rats. 6 ml/kg Sofren Injection restored the RASS indexes of heart failure rats to the level of the normal group.
      CONCLUSION Sofren Injection has the effect of inhibiting the excessive activation of RASS and improving cardiac function. miR-423-5P, miRNA-499 and miR-210-3P can be used as serum markers of CHF.

       

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