CD8^(+)T细胞亚群对小鼠动脉粥样硬化形成的影响及其机制研究  

Effect and mechanism of CD8^(+)T cell subsets on formation of AS in mice

作　　者：张银 朱伟 卢炳军 郜攀 Zhang Yin;Zhu Wei;Lu Bingjun;Gao Pan(Department of Geriatrics and Special Service Medicine,First Affiliated Hospital,Army Medical University,Chongqing 400038,China)

机构地区：[1]陆军军医大学第一附属医院老年医学与特勤医学科,重庆400038

出　　处：《中华老年心脑血管病杂志》2024年第9期1084-1089,共6页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：重庆市自然科学基金(CSTB2022NSCQ-MSX0209)。

摘　　要：目的 探索CD8^(+)T细胞亚群对小鼠动脉粥样硬化(atherosclerosis, AS)形成的影响。方法 通过Lasso回归和随机森林法筛选AS血管关键免疫浸润细胞。构建载脂蛋白E基因(Apolipoprotein E,ApoE)/重组激活基因1(recombination activating gene-1,Rag1)双基因敲除(double knockout, DKO)小鼠,通过高脂喂食构建AS模型。将ApoE基因敲除小鼠分为对照组(Con组)、高脂喂食组(HFD组),每组3只;将ApoE/Rag1 DKO小鼠分为DKO+S组[高脂喂食+磷酸盐缓冲液(phosphate buffer saline, PBS)]、DKO+效应记忆型T细胞(effective memory T cell, Tem)组(高脂喂食联合CD8^(+)Tem回输)及DKO+终末分化Tem(terminal effector memory T cell, Temra)组(高脂喂食联合CD8^(+) Temra回输),每组3只。用油红O染色及苏木精-伊红染色观察Con组、HFD组、DKO+S组、DKO+Tem组及DKO+Temra组小鼠血管壁AS斑块形成情况。结果 Lasso回归和随机森林法结果提示,CD8^(+)Tem是参与班块形成的关键CD8^(+)T细胞类型。油红O染色和苏木精-伊红染色显示,与Con组比较,HFD组AS斑块面积显著增加(P<0.05);HFD组与DKO+S组AS斑块面积比较无显著差异(P>0.05);与DKO+S组比较,DKO+Tem组及DKO+Temra组AS斑块均显著增加(P<0.05)。结论 CD8^(+)T细胞亚群与小鼠AS形成密切相关,CD8^(+)Tem和CD8^(+)Temra显著诱导AS斑块形成。Objective To explore the effect of CD8^(+)T cell subsets on the formation of atherosclerosis(AS) in mice.Methods Lasso regression and random forest were employed to identify key infiltrating immune cells in AS blood vessels.Apolipoprotein E gene(ApoE)/recombination activation gene 1(Rag1) double knockout(ApoE/Rag1-DKO) mice were constructed, and then fed with high-fat chow to establish an AS model.The ApoE knockout mice were divided into control group(Con group) and high-fat diet group(HFD group),with 3 mice in each group.And the ApoE/Rag1-DKO mice were divided into DKO+S group [high-fat diet+phosphate buffer saline(PBS)],DKO+Tem group(high-fat diet with CD8^(+)Tem cell infusion),and DKO+Temra group(high-fat diet with CD8^(+)Temra cell infusion),with 3 mice in each group.Oil red O staining and HE staining were conducted to observe the formation of AS plaques in the vascular walls in the Con, HFD,DKO+S,DKO+Tem, and DKO+Temra groups respectively.Results The results of Lasso regression and random forest showed that CD8^(+)Tem was the most important CD8^(+)T cell subset in the formation of AS.Oil red O staining and HE staining displayed that compared with the Con group, the AS plaque area were significantly larger in the HFD group(P<0.05);compared with the HFD group, there was no significant increase in the AS plaque area in the DKO+S group(P>0.05);compared with the DKO+S group, the AS plaque area were notably increased in the DKO+Tem group and the DKO+Temra group(P<0.05).Conclusion CD8^(+)T cell subsets are closely associated with the formation of AS in mice, and CD8^(+)Tem and CD8^(+)Temra cells significantly induce the formation.

关 键 词：动脉粥样硬化 T淋巴细胞亚群 小鼠 基因敲除 CD8+T细胞亚群 

分 类 号：R543.5[医药卫生—心血管疾病]