Gui Mingtai, Yao Lei, Lu Bo, Li Jianhua, Wang Jing, Zhou Xunjie, Fu Deyu
Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Evid Based Complement Alternat Med. 2022 Mar 10;2022:6400517. doi: 10.1155/2022/6400517. eCollection 2022.
This study aimed to explore the function of modified Yuejuwan (MYJ) on THP-1 macrophage-derived foam cells.
First, human THP-cells were obtained, and then, grouping was made to the following: control group, foaming group, foaming group +0.2 mg/mL Jiawei Yueju pill, foaming group +0.5 mg/mL Jiawei Yueju pill, and foaming group +1 mg/mL Jiawei Yueju pill. An Oil Red O staining assay was used to examine the uptake of oxidatively modified low-density lipoprotein (oxLDL). The secretion of interleukin (IL)-1 and tumor necrosis factor (TNF)- were determined using an enzyme-linked immunosorbent assay (ELISA). Real-time quantitative PCR (qRT-PCR) and Western blot were used to quantify genes and proteins expression levels.
Our results indicated that MYJ inhibited the accumulation of total cholesterol (TC), free cholesterol (FC), and cholesteryl ester (CE) in foam cells. Moreover, the secretion of IL-1 and TNF- also downregulated in foam cells after treatment of MYJ. Furthermore, we found that tripartite motif-containing 37 (TRIM37) was significantly upregulated in foam cells. Knockdown of TRIM37 promoted cholesterol efflux and presented an anti-inflammation effect in foam cells. Furthermore, TRIM37 positively mediated the translocation of NF-B to nuclear. It negatively regulated its ubiquitination in foam cells after interacting with TRAF2. Importantly, MYJ profoundly suppressed the function of TRIM37 in foam cells and functioned as a TRIM37 inhibitor.
This study demonstrated that MYJ might alleviate oxLDL-induced foam cell formation by inhibiting the TRIM37/TRAF2/NF-B pathway activity. MYJ was a potential agent in preventing atherosclerosis and indicated its potential signaling pathway in foam cells.
本研究旨在探讨加味越鞠丸（MYJ）对THP-1巨噬细胞源性泡沫细胞的作用。
首先获取人THP细胞，然后进行分组，分为：对照组、泡沫细胞组、泡沫细胞组+0.2mg/mL加味越鞠丸、泡沫细胞组+0.5mg/mL加味越鞠丸、泡沫细胞组+1mg/mL加味越鞠丸。采用油红O染色法检测氧化修饰低密度脂蛋白（oxLDL）的摄取。使用酶联免疫吸附测定（ELISA）法测定白细胞介素（IL）-1和肿瘤坏死因子（TNF）-的分泌。采用实时定量聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法对基因和蛋白质表达水平进行定量分析。
我们的结果表明，MYJ抑制了泡沫细胞中总胆固醇（TC）、游离胆固醇（FC）和胆固醇酯（CE）的积累。此外，经MYJ处理后，泡沫细胞中IL-1和TNF-的分泌也下调。此外，我们发现含三联基序蛋白37（TRIM37）在泡沫细胞中显著上调。敲低TRIM37可促进胆固醇流出，并在泡沫细胞中呈现抗炎作用。此外，TRIM37正向介导核因子-κB（NF-κB）向细胞核的转位。它与肿瘤坏死因子受体相关因子2（TRAF2）相互作用后，在泡沫细胞中负向调节其泛素化。重要的是，MYJ在泡沫细胞中显著抑制TRIM37的功能，并作为TRIM37抑制剂发挥作用。
本研究表明，MYJ可能通过抑制TRIM37/TRAF2/NF-κB信号通路活性来减轻oxLDL诱导的泡沫细胞形成。MYJ是预防动脉粥样硬化的潜在药物，并表明了其在泡沫细胞中的潜在信号通路。
