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高脂食物和K/BxN血清对ApoE基因敲除小鼠免疫系统的影响 被引量:1

Effect of high fat diet and K/BxN serum on the immune system of ApoE knockout mice
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摘要 目的检测高脂食物和K/BxN血清对ApoE基因敲除(ApoE^(-/-))小鼠免疫细胞分布的影响。方法 ApoE^(-/-)小鼠从8周龄开始饲喂高脂食物,17周龄时腹腔注射抗6-磷酸葡萄糖异构酶(glucose-6-phosphate isomerase,GPI)抗体呈阳性的K/BxN血清,每周注射一次,每次注射0.2 mL。对照组饲喂普通食物,用同样的方法注射K/BxN血清。分别于注射K/BxN血清前后,ELISA法检测小鼠血脂水平变化,游标卡尺测量踝关节肿胀程度。高脂食物和K/BxN血清处理至26周龄时分离脾脏细胞和骨髓细胞,经流式抗体染色后,流式细胞术分析免疫细胞的分布情况。结果 ApoE^(-/-)小鼠腹腔注射K/BxN血清前后,饲喂高脂食物的ApoE^(-/-)小鼠血清低密度脂蛋白胆固醇(LDL-C)浓度,总胆固醇(TCHO)浓度和甘油三酯(TG)浓度均显著升高,主动脉瓣根部斑块面积显著增加,提示无论是否注射K/BxN血清,高脂食物都能使ApoE^(-/-)小鼠产生动脉硬化症状,且比饲喂普通食物的ApoE^(-/-)小鼠更严重。腹腔注射K/BxN血清前,各组ApoE^(-/-)小鼠踝关节和关节炎评分(clinical score)均处于正常水平,腹腔注射K/BxN血清后,饲喂高脂食物的ApoE^(-/-)小鼠踝关节宽度和关节炎评分均低于饲喂普通食物的ApoE^(-/-)小鼠。流式检测结果显示,饲喂高脂食物后注射K/BxN血清使ApoE^(-/-)小鼠脾脏和骨髓的CD3^+T细胞和CD19^+B细胞下调,CD11b^+巨噬细胞上调。结论高脂食物和K/BxN血清引起ApoE^(-/-)小鼠脾脏和骨髓的CD3^+T细胞和CD19^+B细胞下调,CD11b^+巨噬细胞上调,导致ApoE^(-/-)小鼠的动脉硬化症状加重,关节炎症状减轻。 Objective To detect the effect of high fat diet and K/BxN serum on the distribution of immune cells in ApoE gene knockout(ApoE-/-) mice. Methods ApoE-/- mice were fed with high fat diet(HFD) from 8 weeks of age, then the K/BxN serum whose anti-glucose-6-phosphate isomerase(GPI) antibodies were positive was injected intra-peritoneally once a week, with each injection of 0.2 mL, from 17 to 26 weeks of age. The control group was fed with ordinary diet(CD) and injected the K/BxN serum in the same way. The level of blood lipid was analysed by ELISA, and the ankle swelling was measured by vernier caliper before and after the K/BxN serum was injected intra-peritoneally. The splenocytes and bone marrow cells of ApoE-/-mice were isolated and stained by flow antibodies at 26 weeks of age, then detected by flow cytometry. Results Serum LDL-C, TCHO and TG levels of ApoE-/- mice were significantly increased before and after K/BxN serum was injected, and the areas of atherosclerotic plaques were significantly increased in aortic roots after K/BxN serum injected, suggested that whether K/BxN serum was injected, HFD could induce atherosclerosis of ApoE-/- mice, and the atherosclerotic symptom of ApoE-/- mice fed with HFD was more severe than the CD treated group.The ankle width and clinical scores showed that the ankle swelling of ApoE-/- mice was normal before K/BxN serum injected. However, ApoE-/- mice fed with HFD had lower joint width and clinical score than ApoE-/- mice fed with CD after K/BxN serum injected. The flowcytometry analysis showed that HFD down-regulates CD3+T cells and CD19+B cells, up-regulates CD11 b+ macrophages in splenocytes and bone marrow cells. Conclusions HFD down-regulates CD3+T cells and CD19+B cells, up-regulates CD11 b+ macrophages in splenocytes and bone marrow cells, so aggravates the atherosclerosis and relieves arthritis of ApoE-/- mice.
作者 石娜 张抒扬 牛海涛 SHI Na;ZHANG Shuyang;NIU Haitao(NHC Key Laboratory of Human Disease Comparative Medicine(The Institute of Laboratory Animal Sciences,CAMS&PUMC),Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious,Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases,Key Laboratory of Human Diseases Animal Models,State Administration of Traditional Chinese Medicine,Beijing 100021,China;Peking Union Medical College Hospital,Beijing 100010)
出处 《中国比较医学杂志》 CAS 北大核心 2019年第3期21-29,共9页 Chinese Journal of Comparative Medicine
基金 "国家重点研发计划资金资助(2017YFC1103603) "中央高校基本科研业务费专项资金资助(2017310016)
关键词 动脉硬化 关节炎 高脂食物 自身免疫 atherosclerosis arthritis high fat diet autoimmunty
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