强心汤调控IκBα/NF-κBp65信号通路介导的巨噬细胞M1极化治疗慢性心力衰竭的作用机制 点击下载
| 论文标题： | 强心汤调控IκBα/NF-κBp65信号通路介导的巨噬细胞M1极化治疗慢性心力衰竭的作用机制 |
| 英文标题： | |
| 中文摘要： | 目的 探究强心汤调控核因子κB抑制蛋白α/核因子κBp65亚基（IκBα/NF-κBp65）信号通路介导的巨噬细胞M1极化治疗慢性心力衰竭（CHF）的作用机制。方法动物实验以小鼠为研究对象，采用冠状动脉结扎法构建CHF模型，并给予强心汤（21.69g/kg）干预28d；干预结束后，观察小鼠心肌组织病理形态学变化和心肌细胞凋亡情况，检测小鼠血清中炎症因子[肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）]水平以及心肌损伤指标[心肌肌钙蛋白I3（TNNI3）]和巨噬细胞相关标志物[F4/80、分化簇80（CD80）]表达水平。细胞实验以单核巨噬细胞白血病细胞RAW264.7为研究对象，采用10ng/mL脂多糖联合10ng/mLγ干扰素诱导细胞发生M1极化，并给予10%强心汤含药血清干预48h；干预结束后，观察细胞中NF-κBp65、NF-κBp50核转位情况，测定细胞CD80阳性率，检测细胞中炎症因子[IL-1β、IL-6、IL-8、IL-18、TNF-α、诱导型一氧化氮合酶（iNOS）、环氧合酶2（COX2）、C-C基序趋化因子受体7亚型2（CCR7-2）]mRNA以及IκBα/NF-κBp65信号通路相关蛋白表达量。结果动物实验结果显示，强心汤可减轻小鼠心肌组织纤维化程度，显著降低心肌细胞凋亡率和血清中TNF-α、IL-6水平以及心肌组织中TNNI3、F4/80、CD80蛋白表达水平（P＜0.05）。细胞实验结果显示，强心汤可显著减弱细胞中NF-κBp65、NF-κBp50的核转位（P＜0.05）；显著降低细胞CD80阳性率，IL-1β、IL-6、IL-8、IL-18、TNF-α、iNOS、COX2、CCR7-2mRNA表达水平，NF-κBp65的总表达量及细胞核内表达量，磷酸化NF-κBp65的总表达量及细胞核、细胞质内表达量，磷酸化IκBα总表达量（P＜0.05）；显著升高IκBα总表达量和NF-κBp65细胞质内表达量（P＜0.05）。结论强心汤可通过抑制IκBα/NF-κBp65信号通路活性，减少促炎因子释放，从而抑制巨噬细胞M1极化，减轻心肌纤维化，最终发挥治疗CHF的作用。 |
| 英文摘要： | Abstract OBJECTIVE To explore the mechanism of Qiangxin decoction in the treatment of chronic heart failure （CHF） by regulating the inhibitor of nuclear factor-κB alpha/nuclear factor-κB p65 subunit （IκBα/NF-κB p65） signaling pathway-mediated M1 macrophage polarization. METHODS In animal experiments， mice were used as research subjects， and the CHF model was established via coronary artery ligation. Model mice were treated with Qiangxin decoction （21.69 g/kg） for 28 days. After intervention， pathological morphological changes of myocardial tissues and cardiomyocyte apoptosis were observed. Serum levels of inflammatory factors including tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）， myocardial injury marker troponin I3 （TNNI3）， and macrophage-related markers F4/80 and cluster of differentiation 80 （CD80） were detected. In cell experiments， monocyte-macrophage leukemia RAW264.7 cells were induced to undergo M1 polarization by 10 ng/mL lipopolysaccharide combined with 10 ng/mL interferon-γ， followed by 48 h intervention with 10% drug-containing serum of Qiangxin decoction. After intervention， the nuclear translocation of NF-κB p65 and NF-κB p50 was observed. The positive rate of CD80 in cells was measured. The mRNA expression of inflammatory factors including IL-1β， IL-6， IL-8， IL-18， TNF-α， inducible nitric oxide synthase （iNOS）， cyclooxygenase-2 （COX2）， C-C motif chemokine receptor 7 isoform 2 （CCR7-2）， as well as the expression levels of proteins related to the IκBα/NF-κB p65 signaling pathway were detected. RESULTS Animal experimental results showed that Qiangxin decoction alleviated myocardial fibrosis in mice， and significantly reduced the cardiomyocyte apoptosis rate， serum levels of TNF-α and IL-6， as well as the protein expression of TNNI3， F4/80 and CD80 in myocardial tissues （P＜0.05）. Cell experimental results indicated that Qiangxin decoction significantly suppressed the nuclear translocation of NF-κB p65 and NF-κB p50 （P＜0.05）. It significantly decreased the CD80 positive rate， mRNA levels of IL-1β， IL-6， IL-8， IL-18， TNF-α， iNOS， COX2 and CCR7-2， total and nuclear expression of NF-κB p65， total， nuclear and cytoplasmic expression of phosphorylated NF-κB p65， total expression of phosphorylated IκBα （P＜0.05）. Meanwhile， it significantly elevated the total expression of IκBα and cytoplasmic expression of NF-κB p65 （P＜0.05）. CONCLUSIONS Qiangxin decoction can inhibit the activity of the IκBα/NF-κB p65 signaling pathway， reduce the release of pro-inflammatory factors， thereby restraining M1 macrophage polarization， mitigating myocardial fibrosis， and ultimately exerting therapeutic effects against CHF. |
| 期刊： | 2026年第37卷第15期 |
| 作者： | 石炜琦；卢健棋；朱智德；唐梅玲；肖湘；邹珊芸；涂雅柔；胡莉惠 |
| 英文作者： | SHI Weiqi，LU Jianqi，ZHU Zhide，TANG Meiling，XIAO Xiang，ZOU Shanyun，TU Yarou，HU Lihui |
| 关键字： | 强心汤；慢性心力衰竭；IκBα/NF-κB p65信号通路；巨噬细胞M1极化；炎症反应 |
| KEYWORDS： | Qiangxin decoction； chronic heart failure； IκBα/NF-κB p65 signaling pathway； M1 macrophage polarization； inflammatory response |
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