白细胞介素-17抗体对双酚A染毒高脂饲料喂养小鼠脂肪组织巨噬细胞极化的影响  

Effects of interleukin-17 antibody on polarization of macrophages in adipose tissue of high-fat diet fed mice exposed to bisphenol A

作　　者：周义 陆晓桐 罗时猛 李应配 张宇亨 李佐 朱志远 沈彤 Zhou Yi;Lu Xiaotong;Luo Shimeng;Li Yingpei;Zhang Yuheng;Li Zuo;Zhu Zhiyuan;Shen Tong(Department of Occupational and Environmental Health,School of Public Health,Anhui Medical University,Hefei 230032,China)

机构地区：[1]安徽医科大学公共卫生学院职业卫生与环境卫生学系,合肥230032

出　　处：《卫生研究》2021年第5期814-820,共7页Journal of Hygiene Research

基　　金：国家自然科学基金(No.81773467,82073594,81473015);安徽省转化医学研究院科研基金(No.2017zhyx23);国家级大学生创新创业训练计划项目(No.202010366049)。

摘　　要：目的探究白细胞介素(interleukin, IL)-17抗体对双酚A(bisphenol A,BPA)染毒高脂饲料(high-fat diet, HFD)喂养小鼠脂肪组织巨噬细胞(adipose tissue macrophages, ATM)极化的影响。方法 4周龄雄性C57BL/6小鼠,按随机数字表法分为对照组、IgG组、IL-17抗体组、1000 nmol/L BPA组、1000 nmol/L BPA+IgG组、1000 nmol/L BPA+IL-17抗体组,每组8只,HFD喂养,BPA经饮水暴露。IgG组、1000 nmol/L BPA+IgG组腹腔注射100μg IgG抗体,1次/周;IL-17抗体组、1000 nmol/L BPA+IL-17抗体组腹腔注射100μg IL-17抗体,1次/周。16周后处死小鼠,采血分离血清,酶联免疫吸附试验检测瘦素水平;取附睾脂肪组织,免疫组织化学观察IL-1β、IL-6、单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)炎症因子的表达;酶联免疫吸附试验检测诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)、精氨酸合酶1(arginine synthase-1,Arg-1)活性;流式细胞术检测M1、M2型ATM比例;qRT-PCR检测CD11c、CD206 mRNA的表达。结果与对照组相比,1000 nmol/L BPA组小鼠血清瘦素增加,脂肪组织炎症因子IL-6、IL-1β、MCP-1表达上调,M1型ATM比例增加(22.000%±0.500%比31.467%±0.379%),iNOS活性增强,CD11c mRNA表达上调,Arg-1活性减弱,CD206 mRNA表达降低,差异均有统计学意义(P<0.05),但M2型ATMs比例降低不明显(P>0.05);IgG组无显著变化;与1000 nmol/L BPA组相比,1000 nmol/L BPA+IgG组无显著变化;1000 nmol/L BPA+IL-17抗体组小鼠血清瘦素减少,脂肪组织炎症因子IL-6、IL-1β、MCP-1表达下调,M1型ATM比例减少(31.467%±0.379%比22.933%±0.153%),iNOS活性减弱,CD11c mRNA表达下调,M2型ATM比例增加(4.847%±0.655%比7.840%±0.555%),Arg-1活性增强,CD206 mRNA表达上调,差异均有统计学意义(P<0.05)。结论 IL-17抗体可能通过抑制ATM向M1型极化,导致ATM炎性因子的分泌减少,从而改善BPA染毒HFD喂养小鼠的脂肪组织炎症。OBJECTIVE To investigate the effects of interleukin-17(IL-17) antibody on polarization of adipose tissue macrophages(ATM) in mice fed with high-fat diet(HFD) exposed to bisphenol A(BPA). METHODS Four week-old male C57 BL/6 mice were divided into control group, IgG group, IL-17 antibody group, 1000 nmol/L BPA group, 1000 nmol/L BPA+IgG group, and 1000 nmol/L BPA+IL-17 antibody group according to random number table method. Eight mice per group were fed with HFD and BPA was exposed by drinking water.The IgG group and the 1000 nmol/L BPA+IgG group were intraperitoneally injected with 100 μg IgG antibody once a week, and the IL-17 group and the 1000 nmol/L BPA+IL-17 antibody group were intraperitoneally injected with 100 μg IL-17 antibody once a week. After 16 weeks, the mice were sacrificed, and serum samples were collected for serum separation. Leptin level was measured by enzyme-linked immunosorbent assay(ELISA).The expression of IL-1β, IL-6 and monocyte chemoattractant protein-1(MCP-1)inflammatory cytokines were observed by immunohistochemistry(IHC) of adipose tissue of epididymis. The activity of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)was measured by ELISA, and the proportion of M1 and M2 ATMs was measured by flow cytometry(FCM).The expression of CD11 c and CD206 mRNA was measured by qRT-PCR. RESULTS Compared with the control group, serum leptin, the expressions of inflammatory cytokines IL-6, IL-1β and MCP-1 in adipose tissue were increased in 1000 nmol/L BPA group, the proportion of M1 type ATM was increased(22.000%±0.500% vs.31.467%±0.379%), iNOS activity was increased, CD11 c mRNA expression was increased, Arg-1 activity was decreased, CD206 mRNA expression was decreased, the differences were statistically significant(P<0.05), but the proportion of M2 type ATM was decreased insignificantly(P>0.05).There was no significant change in IgG group. Compared with 1000 nmol/L BPA group, IgG+1000 nmol/L BPA group had no significant change. In 1000 nmol/L BPA+IL-17 antibody group, serum leptin

关 键 词：双酚A 白细胞介素-17抗体 巨噬细胞 极化 炎症 

分 类 号：R151.2[医药卫生—营养与食品卫生学] RA114[医药卫生—公共卫生与预防医学]