抗PD-L1单抗促免疫细胞活化参与动脉粥样硬化  

Anti-PD-L1 monoclonal antibody promotes immune cell activation and participates in atherosclerosis

作　　者：李忠莎 李婧玉 魏思萌 李月 李琦[3] 陈畅 LI Zhong-sha;LI Jing-yu;WEI Si-meng;LI Yue;LI Qi;CHEN Chang(Clinical Translational Research Center,Chongqing University Three Gorges Hospital,Chongqing 404100,China;College of Pharmacy,Harbin Medical University;The Biotherapy Center,Harbin Medical University Cancer Hospital,Harbin 150086,China)

机构地区：[1]重庆大学附属三峡医院临床转化研究中心,重庆404100 [2]哈尔滨医科大学药学院药理学教研室 [3]哈尔滨医科大学附属肿瘤医院生物治疗中心,黑龙江哈尔滨150086

出　　处：《中国药理学通报》2023年第9期1633-1637,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No 81970382)。

摘　　要：目的研究抗PD-L1单抗对高脂饮食诱导的ApoE-/-小鼠动脉粥样硬化(atherosclerosis,AS)发生发展的影响。方法将32只ApoE^(-/-)小鼠随机分为正常组、高脂组、正常+抗PD-L1单抗组和高脂+抗PD-L1单抗组,通过高胆固醇饲料喂养建立AS模型。实验动物饲养10周后,分离各组实验动物血管(主动脉根部至胸主动脉),进行油红O染色。酶联免疫吸附法(ELISA)检测血清中总胆固醇(CHO)、三酰甘油(TG)、高密度脂蛋白(HDL-c)、低密度脂蛋白(LDL-c)和炎症因子(IFN-γ、TNF-α、IL-4、IL-13、IL-1β)水平。流式细胞计数检测淋巴细胞(CD3^(+)T、CD4^(+)T和CD8^(+)T)、NK和NKT细胞比例。结果与高脂组相比,给予抗PD-L1单抗后促血管壁脂质累计并上调血清CHO、TG和HDL-c含量,但是对LDL-c无影响。高脂饲养条件下给予抗PD-L1单抗促CD3+、CD4+和CD8+T细胞活化。除此之外,高脂饲养条件下给予抗PD-L1单抗还具有活化NK和NKT细胞的作用。ELISA检测发现,高脂饲养条件下给予抗PD-L1单抗上调血清中炎症因子含量(IFN-γ、TNF-α、IL-4、IL-13、IL-1β)。结论高脂饲养条件下给予抗PD-L1单抗促AS发生发展的机制与免疫活化有关。Aim To study the effect of anti-PD-L1 monoclonal antibody on high-fat diet-induced atherosclerosis in ApoE^(-/-)mice.Methods Thirty-two ApoE^(-/-)mice were randomly divided into normal group,high-fat group,normal+anti-PD-L1 mAb group and high-fat+anti-PD-L1 mAb group.After 10 weeks,the blood samples were harvested,and the blood vessels(aortic root to thoracic aorta)of the experimental animals in each group were separated and stained with Oil Red O.The serum levels of total cholesterol(CHO),triglyceride(TG),high-density lipoprotein(HDL-c),low-density lipoprotein(LDL-c)inflammatory factors(IFN-γ,TNF-α,IL-4,IL-13,IL-1β)were detected by enzyme-linked immunosorbent assay(ELISA).The proportion of lymphocytes(CD3,CD4 and CD8),NK and NKT cells were detected by flow cytometry.Results Compared with the high-fat group,the serum total cholesterol,triglyceride,and high-density lipoprotein of the high-fat+anti-PD-L1 monoclonal antibody group significantly increased,and the lipid deposition was more obvious.At the same time,the plasma CD3^(+),CD4^(+)and CD8^(+)T cells and NK and NKT cells in the high-fat+anti-PD-L1 monoclonal antibody group significantly increased.In addition,serum inflammatory factors(IFN-γ,TNF-α,IL-4,IL-13,IL-1β)in the high-fat treatment group(HFD+Anti-PD-L1)were also significantly elevated.Conclusions Anti-PD-L1 mAb aggravates the progression of atherosclerosis in ApoE-/-mice induced by high-fat diet,which may be related to the activation of immune cells to promote the release of inflammatory factors.

关 键 词：动脉粥样硬化 抗PD-L1单抗 免疫细胞 免疫活化 炎症因子 炎症反应 

分 类 号：R-332[医药卫生] R364.5R392.11R543.5