Wang Qian, Chen Rui, Tang Qian, Chen Jin-Ying, Wang Yan, Sui Dian-Jun, Liu Ai-Dong
The Third Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China.
Changchun University of Traditional Chinese Medicine, Changchun, China.
Evid Based Complement Alternat Med. 2022 Jul 5;2022:1333545. doi: 10.1155/2022/1333545. eCollection 2022.
We have previously reported that flavonoid extract from propolis (FP) can improve cardiac function in rats following myocardial infarction (MI). However, the mechanisms responsible for the cardioprotective effects of FP have not been fully elucidated. In the current study, we explored whether FP can reduce inflammatory cytokines and attenuate sympathetic nerve system activity and antiendoplasmic reticulum (ER) stress and whether the cardioprotective effects are related to peroxisome proliferator-activated receptor gamma (PPAR-) activation. Sprague Dawley rats were randomly divided into six groups: Sham group received the surgical procedure but no artery was ligated; MI group received ligation of the left anterior descending (LAD) branch of the coronary artery; MI + FP group received FP (12.5 mg/kg/d, intragastrically) seven days prior to LAD ligation; FP group (Sham group + 12.5 mg/kg/d, intragastrically); MI + FP + GW9662 group received FP prior to LAD ligation with the addition of a specific PPAR- inhibitor (GW9662), 1 mg/kg/d, orally); and MI + GW9662 group received the PPAR- inhibitor and LAD ligation. The results demonstrated that the following inflammatory markers were significantly elevated following MI as compared with expression in sham animals: IL-1, TNF-, CRP; markers of sympathetic activation: plasma norepinephrine, epinephrine and GAP43, nerve growth factor, thyroid hormone; and ER stress response markers GRP78 and CHOP. Notably, the above changes were attenuated by FP, and GW9662 was able to alleviate the effect of FP. In conclusion, FP induces a cardioprotective effect following myocardial infarction by activating PPAR-, leading to less inflammation, cardiac sympathetic activity, and ER stress.
我们之前曾报道，蜂胶中的类黄酮提取物（FP）可改善大鼠心肌梗死后的心脏功能。然而，FP心脏保护作用的机制尚未完全阐明。在本研究中，我们探究了FP是否能减少炎性细胞因子、减弱交感神经系统活性及抗内质网（ER）应激，以及心脏保护作用是否与过氧化物酶体增殖物激活受体γ（PPAR-γ）激活有关。将Sprague Dawley大鼠随机分为六组：假手术组接受手术操作但未结扎动脉；心肌梗死组接受冠状动脉左前降支（LAD）结扎；心肌梗死+FP组在LAD结扎前7天接受FP（12.5mg/kg/d，灌胃）；FP组（假手术组+12.5mg/kg/d，灌胃）；心肌梗死+FP+GW9662组在LAD结扎前接受FP并添加特异性PPAR-γ抑制剂（GW9662），1mg/kg/d，口服）；心肌梗死+GW9662组接受PPAR-γ抑制剂及LAD结扎。结果表明，与假手术动物相比，心肌梗死后以下炎性标志物显著升高：IL-1、TNF-α、CRP；交感激活标志物：血浆去甲肾上腺素、肾上腺素及GAP43、神经生长因子、甲状腺激素；以及ER应激反应标志物GRP78和CHOP。值得注意的是，上述变化被FP减弱，且GW9662能够减轻FP的作用。总之，FP通过激活PPAR-γ诱导心肌梗死后的心脏保护作用，从而减少炎症、心脏交感神经活性及ER应激。
