Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression
Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression
复制标题
柑橘皮通过上调 PPARγ 表达缓解心肌梗死后心力衰竭
DOI：
10.1111/1440-1681.13642
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发表时间：
2022-03-30
影响因子：
2.9
通讯作者：
Li, Xinli
中科院分区：
文献类型：
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作者：
Chen, Mengli;Zhu, Hongyan;Li, Xinli
心肌梗死（MI）后的心力衰竭是世界范围内的主要死亡原因。白藜芦醇（CRP）是一种传统的中草药，已经在临床上使用了几个世纪。本研究旨在探讨CRP在心肌梗死后心脏重构和心力衰竭中的作用及其分子机制。对8周龄的雄性C57 BL/6小鼠进行冠状动脉结扎以模拟体内临床情况。超声心动图用于评估小鼠心脏的收缩功能。采用Masson三色染色和小麦胚芽凝集素（WGA）染色分别测定小鼠心脏的纤维化面积和横截面积。采用酶消化法从0-3日龄新生大鼠中分离心肌细胞和成纤维细胞。TUNEL法检测细胞凋亡，EdU法检测细胞增殖。通过qRT-PCR分析基因表达变化，并通过Western印迹评估蛋白质表达变化。我们的研究结果表明，CRP减轻心肌肥厚，纤维化和凋亡，减轻心肌梗死后的心力衰竭在体内。此外，CRP减轻心肌细胞凋亡和成纤维细胞增殖和分化成肌成纤维细胞。此外，在体外实验中，PPARγ抑制剂T0070907完全消除了CRP的上述有益作用，而PPARγ激活剂罗格列酮未能进一步改善心脏细胞凋亡和纤维化。CRP可通过激活PPARγ促进心肌肥厚、纤维化和细胞凋亡，改善MI后心力衰竭。
Heart failure after myocardial infarction (MI) is the leading cause of death worldwide. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese herbal medicine that has been used in the clinic for centuries. In this study, we aimed to investigate the roles of CRP in cardiac remodelling and heart failure after MI, as well as the molecular mechanisms involved. Male C57BL/6 mice aged 8 weeks were subjected to coronary artery ligation to mimic the clinical situation in vivo. Echocardiography was used to assess the systolic function of the mouse heart. Masson trichrome staining and Wheat germ agglutinin (WGA) staining were utilised to determine the fibrotic area and cross‐sectional area of the mouse heart, respectively. Cardiomyocytes and fibroblasts were isolated from neonatal rats aged 0–3 days in vitro using enzyme digestion. TUNEL staining and EdU staining were performed to evaluate apoptosis and proliferation, respectively. Gene expression changes were analysed by qRT–PCR, and protein expression changes were assessed by Western blotting. Our findings revealed that CRP attenuated cardiac hypertrophy, fibrosis and apoptosis and alleviated heart failure after MI in vivo. Furthermore, CRP mitigated cardiomyocyte apoptosis and fibroblast proliferation and differentiation into myofibroblasts. In addition, the PPARγ inhibitor T0070907 completely abolished the abovementioned beneficial effects of CRP, and the PPARγ activator rosiglitazone failed to further ameliorate cardiac apoptosis and fibrosis in vitro. CRP alleviates cardiac hypertrophy, fibrosis, and apoptosis and can ameliorate heart failure after MI via activation of PPARγ.