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骨髓源性生长因子缺失导致小鼠心肌梗死后纤维化加剧

Loss of Myeloid-Derived Growth Factor Leads to Increased Fibrosis in Mice After Myocardial Infarction

    摘要
  • 摘要:
    目的 研究心梗后骨髓源性生长因子（myeloid-derived growth factor, Mydgf）的缺失对心肌成纤维细胞活化的作用。
    方法 取成年野生型（wild type, WT）小鼠与Mydgf敲除（myeloid-derived growth factor knockout, Mydgf-KO）小鼠，检验这两组小鼠的心功能指标左室射血分数（left ventricular ejection fraction, LVEF）和左室短轴缩短率（left ventricular fractional shortening, LVFS）（n=10），实时定量PCR（quantitative real-time PCR, qRT-PCR）（n=3）检测肌成纤维细胞标志物α-平滑肌肌动蛋白（α-SMA）、骨膜蛋白（postn）、Ⅷ型胶原（type Ⅷ collagen, col8al）、结缔组织生长因子（connective tissue growth factor, ctgf）的mRNA表达水平，Western blot（n=3）检测肌α-SMA的蛋白表达水平；对WT与Mydgf-KO小鼠造心肌梗死（myocardial infarction, MI）模型，检测小鼠术后LVEF和LVFS（n=10），取出心脏后进行Masson染色测定梗死面积（n=10）。分别在MI后第7天、第14天收集Mydgf-KO及WT小鼠的心脏，验证肌成纤维细胞标志物（n=3）的表达情况。
    结果 相较于WT小鼠，Mydgf-KO成年小鼠LVEF、LVFS无明显变化（P均>0.05），但α-SMA和postn的mRNA水平上调，α-SMA蛋白表达水平增加（P均<0.05）；MI后，与WT小鼠相比，Mydgf-KO小鼠LVEF、LVFS下降，且梗死面积增大（P均<0.05）；进一步发现，Mydgf-KO小鼠α-SMA、col8al、postn和ctgf的mRNA水平升高，同时α-SMA蛋白表达水平上调且α-SMA阳性的成纤维细胞增加（P均<0.05）。
    结论 Mydgf缺失促使心脏成纤维细胞转变为肌成纤维细胞，同时也加剧心梗后的纤维化。

     

    Abstract:
    Objective To investigate the effect of the loss of myeloid-derived growth factor (Mydgf) on the transformation of cardiac fibroblasts into myofibroblasts after myocardial infarction (MI).
    Methods Two adult mouse groups, including a wild-type (WT) group and another group with Mydgf knockout (Mydgf-KO), were examined in the study. The mice in these two groups were tested for their cardiac function by measuring left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (n=10). Quantitative real-time PCR (qRT-PCR) (n=3) was performed to determine the mRNA expression levels of myofibroblast markers, including α-smooth muscle actin (α-SMA), periostin (postn), type Ⅷ collagen (col8al), and connective tissue growth factor (ctgf). Western blot (n=3) was performed to verify the protein expression levels of α-SMA. MI modeling was performed on the WT and the Mydgf-KO mice. Postoperative LVEF and LVFS (n=10) were then measured. The hearts were harvested and Masson staining was performed to determine the infarcted area (n=10). The heart samples of Mydgf-KO and WT mice were collected at d 7 and d 14 after MI, respectively, to verify the expression of myofibroblast markers (n=3).
    Results Compared with WT mice, LVEF and LVFS in adult Mydgf-KO mice showed no significant changes (all P>0.05). However, the mRNA levels of α-SMA and postn were upregulated, and α-SMA protein expression was also increased (all P<0.05). After MI, compared with WT mice, LVEF and LVFS in Mydgf-KO mice decreased, and the infarcted area increased significantly (all P<0.05). Furthermore, mRNA levels of α-SMA, col8al, postn, and ctgf were increased in Mydgf-KO mice. In addition, the α-SMA protein expression level was upregulated and α-SMA-positive fibroblasts were increased (P<0.05).
    Conclusion Mydgf deletion promotes the transformation of cardiac fibroblasts into myofibroblasts and aggravates myocardial fibrosis after MI.

     

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