Cai Liang, Tang Hanfei, Zhou Min, Ding Yong, Li Xu, Shi Zhenyu
Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China..
J Surg Res. 2021 Nov;267:404-413. doi: 10.1016/j.jss.2021.05.001. Epub 2021 Jul 2.
The inflammatory reaction is an important mechanism of pathogenesis of abdominal aortic aneurysm (AAA). Artesunate (AS) has been found to have anti-inflammatory effects in cardiovascular disease. The purpose of this study was to investigate whether AS could inhibit the development of AAA.
AngII infused ApoE (-/-) male mice were selected as AAA model. Mice were spilt into three groups, the experimental control group (AngII), the AS treatment group (AngII + AS) and the negative control group (Vehicle) with 14 in each group. Daily administration of AS (100 mg/kg/d) or vehicle performed 3 day before the perfusion. At the end of the 28-day experiment, animal ultrasound and electronic digital caliper were used to measure the diameter of abdominal aorta. Histologic assays were performed to observe the microstructure of the aorta wall. Immunofluorescence staining was performed to detect inflammatory cells, as well as the levels of matrix metalloproteinases (MMPs). The transcription of cytokines and adhesion molecules were investigated by real-time fluorescence quantitative PCR (qPCR). Western blotting was performed to determine whether the NF-κB pathway is involved in the mechanism.
While AS failed to reduce the incidence of AAA, AS effectively reduced the diameter of AAA independently of blood pressure effects. Immunofluorescence detection showed that AS effectively reduced the levels of CD45+ cells and MAC3+ macrophages as well as MMP-2 and MMP-9. qPCR revealed that AS reduced mRNA transcription levels of MMP-2, MMP-9, the cytokine IL-1β, TNF-α, adhesion molecules ICAM-1, VCAM-1. AS decreased the levels of NF-κB signaling pathway in aorta.
AS can attenuate the development of AAA in mice. The possible mechanism is anti-inflammation.
炎症反应是腹主动脉瘤（AAA）发病机制的重要机制。青蒿琥酯（AS）已被发现对心血管疾病具有抗炎作用。本研究的目的是探讨AS是否能抑制AAA的发展。
选择AngII灌注的ApoE（-/-）雄性小鼠作为AAA模型。将小鼠分为三组，即实验对照组（AngII）、AS治疗组（AngII + AS）和阴性对照组（Vehicle），每组14只。在灌注前3天每天给予AS（100 mg/kg/d）或赋形剂。在28天实验结束时，使用动物超声和电子数字卡尺测量腹主动脉直径。进行组织学分析以观察主动脉壁的微观结构。进行免疫荧光染色以检测炎症细胞以及基质金属蛋白酶（MMPs）的水平。通过实时荧光定量PCR（qPCR）研究细胞因子和粘附分子的转录。进行蛋白质免疫印迹法以确定NF-κB途径是否参与该机制。
虽然AS未能降低AAA的发生率，但AS有效地降低了AAA的直径，且与血压效应无关。免疫荧光检测显示，AS有效地降低了CD45+细胞和MAC3+巨噬细胞的水平以及MMP-2和MMP-9的水平。qPCR显示，AS降低了MMP-2、MMP-9、细胞因子IL-1β、TNF-α、粘附分子ICAM-1、VCAM-1的mRNA转录水平。AS降低了主动脉中NF-κB信号通路的水平。
AS可减轻小鼠AAA的发展。可能的机制是抗炎作用。
