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| 基于AMPK/mTOR信号通路探究阿托伐他汀对川崎病冠状动脉内皮细胞损伤的影响 |
| Effect of atorvastatin regulating AMPK/mTOR signaling pathway on coronary endothelial cell injury in Kawasaki disease and its mechanism |
| 投稿时间：2024-11-12 |
| DOI：10.3969/j.issn.1000-0399.2025.07.001 |
| 中文关键词: 阿托伐他汀 川崎病 冠状动脉内皮细胞 炎症 自噬 AMP活化蛋白激酶 |
| 英文关键词: Atorvastatin Kawasaki disease Coronary endothelial cells Inflammation Autophagy AMP activates protein kinase |
| 基金项目:湖北省儿科联盟医学科研项目（编号：HPAMRP202408） |
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| 中文摘要: |
| 目的 探究阿托伐他汀对AMPK/mTOR信号通路的调节作用，以及对川崎病（KD）冠状动脉内皮细胞损伤的影响。方法 体外培养人冠状动脉内皮细胞（HCAEC），利用肿瘤坏死因子α（TNF-α）刺激模拟KD的局部炎性病变，建立KD细胞模型。将细胞分为对照组、TNF-α刺激组、TNF-α+阿托伐他汀10 μmol/L（低剂量）组和TNF-α+阿托伐他汀100 μmol/L（高剂量）组。检测各组炎症和自噬相关因子表达水平以及AMPK/mTOR信号通路变化。结果 TNF-α处理抑制HCAEC细胞增殖活力，加入阿托伐他汀导致了相反的结果。与对照组相比，TNF-α组中白细胞介素（IL）-1β和IL-6的表达水平升高，而阿托伐他汀能够逆转这一趋势，且高剂量阿托伐他汀组逆转效果更为明显（P均＜0.05）。高剂量阿托伐他汀能够逆转TNF-α引起的LC3、Beclin-1、p-AMPK/AMPK下调和P62、p-mTOR/mTOR上调（P均＜0.05），但低剂量阿托伐他汀不能逆转这种表现（P＞0.05）。结论 高剂量阿托伐他汀可通过AMPK/mTOR途径激活自噬进而产生抗炎作用，减轻TNF-α诱导的KD细胞模型中的内皮细胞损伤。 |
| 英文摘要: |
| Objective To explore the role of atorvastatin in regulating AMPK/mTOR signaling pathway, and the effect of atorvastatin on coronary endothelial cell injury in Kawasaki disease (KD) and the underlying mechanism.Methods Human coronary endothelial cells (HCAEC) were cultured in vitro, and the KD cell model was established by using tumor necrosis factor α (TNF-α) to stimulate the local inflammatory lesions of KD. The cells were divided into the control group, TNF- α stimulation group, TNF- α + atorvastatin 10 μmol/L (low dose) group and TNF-α+atorvastatin 100 μmol/L (high dose) group. The expression levels of cytokines related to inflammation and autophagy, and the changes of AMPK/mTOR signaling pathway were detected in each group.Results TNF-α treatment significantly inhibited cell proliferation activity, and atorvastatin addition resulted in the opposite effect. Compared with the control group, the expression levels of IL-1β and IL-6 significantly increased in the TNF-α group, and atorvastatin could significantly reverse this trend, and the improvement was more significant in the high-dose atorvastatin group. High doses of atorvastatin significantly reversed TNF-α-induced down-regulation of LC3, Beclin-1 and pAMPK/AMPK, up-regulation of P62 and p-mTOR/mTOR, but low doses of atorvastatin did not reverse this performance.Conclusion Atorvastatin can significantly reduce endothelial cell injury in TNF- α-induced KD cell model through anti-inflammatory and anti-autophagy effects of AMPK/mTOR pathway. |
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