生脉注射液通过miR-21调控内质网应激抑制心肌梗死后心肌纤维化

    Shengmai Injection suppresses endoplasmic reticulum stress caused myocardial fibrosis by controlling miR-21 expression in cardiac fibroblasts

      摘要
    • 摘要:
      目的 探讨和监测生脉注射液对心梗后心衰小鼠心肌纤维增殖的抑制效果，同时阐明其可能的治疗机制。
      方法 建立心肌梗死后的心衰模型和AngⅡ模型。超声心电图评估心衰小鼠的心脏功能和结构。Masson染色法评估心衰小鼠心肌纤维化的程度。RT-qPCR检测心肌组织和细胞中miR-21、COL1A1 mRNA和COL3A1 mRNA的表达。Western blot定量分析心肌组织和细胞中增强子结合蛋白同源蛋白 (CCAAT enhancer binding protein homologous protein，CHOP)、葡萄糖调节蛋白78 (glucose regulated protein 78，GRP78) 和caspase-12蛋白的表达情况。
      结果 通过心肌组织Masson染色技术发现，生脉注射液能有效地减缓心肌梗死后小鼠心肌纤维化的进程，并降低心肌组织中miR-21、GRP78、CHOP以及caspase-12的表达（P<0.05, P<0.01）。此外，细胞实验观察到AngⅡ能显著促进心肌成纤维细胞(cardiac fibroblasts, CFs) 和心脏微血管内皮细胞 (cardiac microvascular endothelial cells, CMECs) 的增殖（P<0.01），并上调CFs中COL1A1、COL3A1、miR-21、GRP78、CHOP及caspase-12的表达（P<0.01）。抑制miR-21后，CFs中COL1A1、COL3A1、GRP78、CHOP及caspase-12的表达水平显著下降（P<0.05）；生脉注射液则可下调COL1A1、COL3A1、miR-21、GRP78、CHOP及caspase-12表达（P<0.05），抑制CFs增殖和胶原合成（P<0.05）。
      结论 给予小鼠生脉注射液，可以有效抑制心肌梗死后心肌纤维化的发生，其机制与降低CFs上miR-21表达抑制内质网应激有关。

       

      Abstract:
      AIM To investigate the effects of Shengmai Injection in a mouse model of heart failure caused by myocardial infarction and whether it reduced fibrosis.
      METHODS  Myocardial infarction model and Angiotensin II (Ang II) model were established. Echocardiography was conducted to evaluate the cardiac function and structure in mice and myocardial fibrosis was evaluated with Masson staining. RT-qPCR was used to measure the levels of miR-21, COL1A1 mRNA and COL3A1 mRNA, while Western blot was employed to measure GRP78, CHOP and caspase-12 levels in both cardiac tissue and cardiac fibroblasts (CFs).
      RESULTS  Masson staining of myocardial tissue, found that Shengmai injection can effectively slow the progression of myocardial fibrosis in mice after myocardial infarction and reduce the expression of miR-21, GRP78, CHOP, and caspase-12 (P<0.05, P<0.01). Additionally, cell experiments showed that Ang II significantly promotes the proliferation of cardiac fibroblasts (CFs) and cardiac microvascular endothelial cells (CMECs) (P<0.01), and upregulates the expression of COL1A1, COL3A1, miR-21, GRP78, CHOP, and caspase-12 in CFs (P<0.01). After inhibiting miR-21, the expression levels of COL1A1, COL3A1, GRP78, CHOP, and caspase-12 in CFs significantly decreased (P<0.05); Shengmai injection can also downregulate the expression of COL1A1, COL3A1, miR-21, GRP78, CHOP, and caspase-12 (P<0.05), inhibit the proliferation of CFs, and collagen synthesis (P<0.05).
      CONCLUSION  The administration of Shengmai injection effectively reduces myocardial fibrosis in mice with heart failure following a myocardial infarction by regulating miR-21 expression and diminishing reticulum stress in cardiac fibroblasts.

       

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