Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy.
Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy.
复制标题
中药通心络通过增强 Beclin-1 诱导的自噬减轻 Ox-LDL 刺激的巨噬细胞中的脂质沉积
DOI：
10.3389/fphar.2021.673366
复制
发表时间：
2021
影响因子：
5.6
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Chen Y;Yu F;Zhang Y;Li M;Di M;Chen W;Liu X;Zhang Y;Zhang M
通心络（TXL）是一种传统中药，在动脉粥样硬化斑块的形成和发展中起着关键作用。巨噬细胞形成泡沫细胞加速斑块的不稳定。在以往的研究中，我们发现通心络通过促进Beclin-1-Bcl-2复合物的解离，显著抑制ox-LDL诱导的体外巨噬细胞凋亡。因此，本研究探讨通心络对巨噬细胞脂质代谢的影响及其机制。为探讨通心络在动脉粥样硬化斑块形成中的作用，本研究采用慢病毒注射法建立动脉粥样硬化动物模型，并进行体内免疫荧光染色分析。通过Western blot、免疫荧光染色和显微镜观察等方法，探讨川芎素对THP-1巨噬细胞自噬的调控机制。免疫荧光检测显示通心络治疗可抑制晚期动脉粥样硬化斑块中的脂质沉积。体外TXL处理通过Beclin-1增强自噬抑制THP-1巨噬细胞中的脂质沉积。通心络可逆转ox-LDL诱导的组蛋白去乙酰化酶（HDACs）的高表达（p <0.05）。与TXL + ox-LDL组相比，TXL组在加入组蛋白去乙酰化酶激动剂后未能促进细胞内脂滴的分解。我们发现通心络通过增强Beclin-1诱导的自噬来减弱巨噬细胞中脂质的积累，此外，它抑制I类HDAC对Beclin-1表达的抑制作用。
Tongxinluo (TXL), a traditional Chinese medication, plays a key role in the formation and progression of plaques in atherosclerosis. The formation of foam cells by macrophages accelerates the destabilisation of plaques. In previous research, we had found that TXL significantly inhibits ox-LDL-induced apoptosis in macrophages in vitro by improving the dissociation of the Beclin-1-Bcl-2 complex. Therefore, here, we explored the effect of TXL on lipid metabolism in macrophages and the mechanism involved. To evaluate the role of TXL in atherosclerotic plaques, we construct the atherosclerotic animal model with lentiviral injection and performed immunofluorescence staining analysis in vivo. Western blot, immunofluorescence staining and microscopy were performed to elucidate the mechanism underlying TXL-mediated regulation of autophagy in THP-1 macrophages in vitro. Immunofluorescence assay revealed that TXL treatment inhibited lipid deposition in advanced atherosclerotic plaques. In vitro TXL treatment inhibited lipid deposition in THP-1 macrophages by enhancing autophagy via Beclin-1. TXL reversed the high expression of class I histone deacetylases (HDACs) induced by ox-LDL (p < 0.05). Compared with the TXL + ox-LDL group, TXL failed to promote intracellular lipid droplet decomposition after the addition of the histone deacetylase agonist. We found that TXL attenuates the accumulation of lipids in macrophage by enhancing Beclin-1-induced autophagy, and additionally, it inhibits the inhibitory effect of class I HDAC on the expression of Beclin-1.
登录
查看更多内容
影响因子：
6.1
作者：
Zhang L;Li Y;Yang BS;Li L;Wang XZ;Ge ML;Jing QM;Ma YY;Wang G;Liu HW;Zhao X;Wang B;Xu K;Han YL
通讯作者：
Han YL
DOI：
10.1038/nri3520
发表时间：
2013-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.8
作者：
Orsó, E;Broccardo, C;Schmitz, G
通讯作者：
Schmitz, G
影响因子：
64.8
作者：
Singh, Rajat;Kaushik, Susmita;Wang, Yongjun;Xiang, Youqing;Novak, Inna;Komatsu, Masaaki;Tanaka, Keiji;Cuervo, Ana Maria;Czaja, Mark J.
通讯作者：
Czaja, Mark J.
影响因子：
7.5
作者：
Maxfield FR;van Meer G
通讯作者：
van Meer G