Abstract:
This study was to investigate the therapeutic effect of Bacillus amyloliquefaciens (Ba) on atherosclerosis (AS). THP-1 monocyte was differentiated to THP-1 macrophage (THP-M) through phorbol 12-myristate 13-acetate. After pre-treatment by 108 cfu/ml Ba lasting 6 h, THP-M was induced with 100 mg/l ox-LDL lasting 48 h to form macrophage foam cell (THP-F). RT-qPCR and flow cytometry were employed to determine the polarization of THP-M and THP-F. ApoE-/- mice with high-fat and high-cholesterol diet were used for constructing an AS model to evaluate the effect of Ba on AS. Our in vitro results showed that Ba vegetative cells pre-treatment distinctly inhibited the levels of iNOS and CD16/CD32 (M1 macrophage markers), and increased the levels of FIZZ1, Ym1, Arg1, CD163, and CD206 (M2 macrophage markers), indicating that Ba pre-treatment promoted anti-inflammatory M2-like polarization both in THP-M and THP-F. Meanwhile, it also suppressed cholesterol uptake, esterification, and hydrolysis, and efflux by THP-M and THP-F. Additionally, our animal experiments demonstrated that Ba vegetative cells treatment suppressed high cholesterol, hyperglycemia, hyperlipidemia, and the release of inflammatory factors (TNF-α, IL-6 and IL-1β) in ApoE-/- AS mice. In a word, our results indicated that Ba may protect against AS through alleviating foam cell formation and macrophage polarization through targeting certain stages of AS.
摘要:
本研究旨在探讨解淀粉芽孢杆菌(Ba)对动脉粥样硬化(AS)的治疗作用。THP-1单核细胞通过佛波醇12-肉豆蔻酸酯13-乙酸酯分化为THP-1巨噬细胞(THP-M)。用108cfu/mlBa预处理6h后,用100mg/lox-LDL持续48h诱导THP-M形成巨噬细胞泡沫细胞(THP-F)。RT-qPCR和流式细胞术用于确定THP-M和THP-F的极化。采用高脂高胆固醇饮食的ApoE-/-小鼠构建AS模型,评价Ba对AS的影响。我们的体外结果表明,Ba营养细胞预处理明显抑制iNOS和CD16/CD32(M1巨噬细胞标记)的水平,并增加FIZZ1,Ym1,Arg1,CD163和CD206(M2巨噬细胞标记)的水平,表明Ba预处理促进THP-M和THP-F的抗炎M2样极化。同时,它还抑制了胆固醇的摄取,酯化,和水解,THP-M和THP-F流出此外,我们的动物实验表明,Ba营养细胞治疗抑制了高胆固醇,高血糖症,高脂血症,和炎症因子(TNF-α,ApoE-/-AS小鼠中的IL-6和IL-1β)。一句话,我们的结果表明,Ba可能通过靶向AS的某些阶段来减轻泡沫细胞的形成和巨噬细胞的极化来预防AS。