双酚A诱导肥胖小鼠中脂肪组织巨噬细胞聚集

Accumulation of adipose tissue macrophages in obese mice induced by bisphenol A

目的研究饮水摄入低剂量双酚A(BPA)诱导的肥胖小鼠中脂肪组织巨噬细胞的聚集。方法将4周龄雄性C57BL/6小鼠随机分为正常饮食(ND)组和高脂饮食(HFD)组,每组再分别设溶剂对照组、10 nmol/L BPA组、100 nmol/L BPA组和1 000 nmol/L BPA组。小鼠经饮水摄取BPA,20周后称量体重,处死,无菌取附睾脂肪垫,HE染色观察脂肪组织炎性细胞浸润,免疫组化法检测脂肪组织IL-6的表达,流式细胞术分析脂肪组织血管基质成分(SVF)巨噬细胞比例。结果与各自对照组比较,ND和HFD小鼠BPA暴露组体重和附睾脂肪垫系数明显升高(P<0.05),且随BPA剂量的增加而上升(P<0.05);BPA暴露组脂肪组织脂肪细胞体积和细胞间隙增大,间隙有炎细胞浸润;BPA暴露可致脂肪组织炎性因子IL-6表达上调和附睾脂肪垫SVF中巨噬细胞比例明显升高(P<0.05)。结论低剂量BPA暴露可以诱导小鼠肥胖,而脂肪组织巨噬细胞的聚集可能与BPA诱导肥胖相关。

Objective To investigate the accumulation of macrophages in the adipose tissue from the obese mice in- duced by low -dose bisphenol A （BPA） intake through potable water. Methods Four-week C57BL/6 male mice were randomly divided into normal diet （ND） group and high fat diet （HFD） group. Each group was further divid- ed into vehicle control, 10 nmol/L BPA, 100 nmol/L BPA and 1 000 nmoL/L BPA group. Mice were exposed to BPA through drinking water. After 20 weeks, mice were weighed and sacrificed. The epididymis fat pad was ob- tained under sterile conditions. The infiltration of inflammatory cells in adipose tissues were observed by hematoxy- lin-eosin （HE） staining. IL-6 expression in adipose tissues was detected by immunohistochemistry. The proportion of macrophages in stromal vascular fractions （SVF） was analyzed by flow cytometry. Results In ND and HFD groups, the body weight and coefficients of epididymis fat pad in BPA exposed mice were significantly increased compared with the corresponding control, and as a dose-dependent manner. The volumes of adipocytes and gap be- tween adipocytes were exaggerated. Infiltration of inflammatory cells in adipose tissue was observed in BPA treated mice. In addition, BPA exposure upregulated IL-6 expression in adipose tissue and elevated the percentages of macrophages in SVF. Conclusion Low-dose BPA exposure can induce obesity in mice, which is associated with the accumulation of macrophages in adipose tissue.