Modulating Neuro-Immune-Induced Macrophage Polarization With Topiramate Attenuates Experimental Abdominal Aortic Aneurysm
Modulating Neuro-Immune-Induced Macrophage Polarization With Topiramate Attenuates Experimental Abdominal Aortic Aneurysm
复制标题
DOI：
10.3389/fphar.2020.565461
复制
发表时间：
2020-08-28
影响因子：
5.6
通讯作者：
Liu, Jinping
中科院分区：
文献类型：
--
作者：
Chen, Xing;Li, Yang;Liu, Jinping
腹主动脉瘤（AAA）的发展可归因于心理和生理因素。托吡酯是GABA(A)受体的激动剂，对神经元疾病有贡献，并部分参与免疫调节，可能对腹主动脉瘤的进展有效。我们采用实验性腹主动脉瘤模型：血管紧张素II （Ang II）诱导的ApoE（-/-）雄性小鼠（Ang II/ ApoE模型）。在Ang II/APOE模型中，所有小鼠（n=64）分为4组：假手术组（PBS治疗）、对照组（Ang II治疗）、低剂量组（Ang II +低剂量托吡酯，3 mg/d /只小鼠）、高剂量组（Ang II +高剂量托吡酯，6 mg/d /只小鼠）。所有的治疗都在手术后的第二天开始。收集组织和培养细胞进行组织学和生化检查。体外研究了托吡酯对LPS刺激下骨髓源性巨噬细胞的影响。我们的数据表明，在体内和体外，托吡酯治疗显著促进巨噬细胞保存和巨噬细胞M1向M2表型的转化。因此，M1巨噬细胞介导的促炎活性降低，M2巨噬细胞介导的修复过程增强。低剂量组和高剂量组腹主动脉瘤发生率分别为50%和37.5%，而对照组为75%。托吡酯是一种很有前景的心理疾病药物，靶向神经免疫诱导的巨噬细胞极化，可能会减轻实验性腹主动脉瘤的进展。
The development of abdominal aortic aneurysm (AAA) is attributed to psychological and physical factors. Topiramate, which is an agonist of the GABA(A)receptor, makes contributions to neuronal disease and is partially involved in immune regulation, may be effective upon abdominal aortic aneurysm progression. We used experimental abdominal aortic aneurysm models: Angiotensin II (Ang II)-induced ApoE(-/-)male mice (Ang II/APOE model) in our study. In the Ang II/APOE model, all mice (n=64) were divided into four groups: sham group (PBS treatment), control group (Ang II treatment), low-dose group (Ang II + low-dose topiramate, 3 mg/day per mouse), and high-dose group (Ang II + high-dose topiramate, 6 mg/day per mouse). All treatments began on the day after surgery. Moreover, collected tissues and cultured cell were used for histology and biochemical examination.In vitro, the effects of topiramate on bone marrow-derived macrophage stimulated by LPS were investigated. Our data implied that topiramate treatment significantly promoted macrophages preservation and conversion of M1 to M2 macrophage phenotypesin vivoandin vitro. Accordingly, proinflammatory activities mediated by the M1 macrophages were decreased and the repair process mediated by M2 macrophages was enhanced. The low-dose and high-dose groups had abdominal aortic aneurysm incidences of 50% and 37.5%, respectively, compared with 75% in the control group. Topiramate, a promising drug for the psychological disease, that target neuro-immune-induced macrophage polarization may attenuate experimental abdominal aortic aneurysm progression.