Protective effect of hydroxychloroquine on rheumatoid arthritis-associated atherosclerosis

查看全文 作　　者：Na [1]Shi;Shuangyue [1]Zhang;Gregg [2]Silverman;Mengtao [3]Li;Jun [4]Cai;Haitao [1]Niu

机构地区：[1]NHC Key Laboratory of Human Disease Comparative Medicine (The Institute of Laboratory Animal Sciences, CAMS&PUMC), Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing, China;[2]Department of Rheumatology, Langone Medical Center, New York University, New York City, New York;[3]Peking Union Medical College Hospital, Beijing, China;[4]Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China

出　　处：《Animal Models and Experimental Medicine》索引2019年第2卷第2期,共9页

基　　金：supported by CAMS Initiative for Innovative Medicine of China,Grant/Award Number:No.2016-12M-1-006;National Key R&D Program of China,Grant/Award Number:No.2017YFC1103603 摘　　要：Background: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis. Methods: We created three groups of K/BxN female mice that were positive for the anti‐glucose‐6‐phosphate isomerase (GPI) antibody: control diet (CD), high fat diet (HFD), and HFD with hydroxychloroquine (HFD + HCQ). Serological tests were used to detect the serum levels of total cholesterol (TCHO), low‐density lipoprotein cholesterol (LDL‐C), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), anti‐ GPI antibody titers, and serum cytokines. Atherosclerotic plaque was determined by histological analysis, and gut microbiota were determined by 16sV4 sequencing. Results: Relative to mice given the CD, those receiving the HFD had increased serum levels of LDL‐C, TCHO, and TG, decreased serum levels of HDL‐C, increased atherosclerotic lesions in the aortic root, and altered gut microbiota. Addition of HCQ to HFD decreased the serum levels of LDL‐C, TCHO, and TG, increased serum levels of HDL‐C, and decreased the atherosclerotic lesions in the aortic root. Mice receiving HFD + HCQ also had the greatest bacterial diversity among the three experimental groups. Moreover, HCQ treatment significantly increased the abundance of Akkermansia and Parabacteroides, and decreased the abundance of Clostridium sensu stricto cluster 1, and therefore may be responsible for the reduced RA‐associated atherosclerosis and dyslipidemia. Conclusion: Our mouse model of RA indicated that HFD increased ankle width and aggravated a therosclerosis a nd d yslipidemia, a nd t hat H CQ a lleviated t he d yslipidemia and atherosclerosis, but had no effect on ankle width. 关键词：ATHEROSCLEROSIS AUTOIMMUNITY HYDROXYCHLOROQUINE intestinal MICROBIOTA RHEUMATOID ARTHRITIS

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Protective effect of hydroxychloroquine on rheumatoid arthritis-associated atherosclerosis

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