调节性T细胞在小鼠肥胖早期的数量变化及其对内脏脂肪巨噬细胞亚型的调节作用

Changes of Regulatory T Cells in the Early Stage of Obesity Mice and Their Modulation on Macrophage Subtypes in Visceral Adipose Tissue

目的探讨调节性T细胞(Tregs)在肥胖小鼠的变化及其对脂肪巨噬细胞的调节。方法建立C57BL/6小鼠的肥胖模型,分别在4、10和20周龄观察代谢指标,脾脏内Tregs和脂肪组织内M1/M2型巨噬细胞的数量。用雷帕霉素干预肥胖小鼠,观察其刺激Tregs后对代谢和脂肪炎症的影响。结果 C57BL/6小鼠在20周龄时建成早期肥胖模型,肥胖组小鼠的附睾旁脂肪质量和瘦素水平显著高于对照组(P<0.05),但两组血糖和胰岛素水平差异均无统计学意义(P均>0.05),同时,肥胖小鼠脂肪巨噬细胞数量增加,而Tregs呈下降趋势。雷帕霉素干预可使脾脏内Tregs数量显著增加,且伴有代谢紊乱的改善和脂肪M1/M2比例降低。结论肥胖早期Tregs数量的下降可能与脂肪巨噬细胞的浸润及亚型分布异常有关。

Objective To investigate the changes of regulatory T cells（ Tregs） and whether Tregs can modulate the distribution of macrophage subtypes in visceral adipose tissue in the early stage of obesity.Methods After C57 BL/6 mice obesity models were successfully established,metabolic parameters and numbers of Tregs and M1/M2 macrophage were measured at 4,10,and 20 weeks. The changes of metabolic parameters and adipose tissue inflammation in obesity mice after rapamycin intervention were evaluated. Results The earlystage obesity models were successfully established. Compared with normal diet mice,high fat diet mice had significantly higher epididymal adipose tissue mass and serum leptin levels（ P〈0. 05）. However,there was no statistical difference in blood glucose and insulin levels between these two groups（ All P〉0. 05）. Macrophagesinfiltration in adipose tissue in high fat diet mice gradually increased with time,coincident with decrease in Treg numbers. Increased numbers of Treg,improved metabolic parameters, and decreased ratio of M1/M2 can be seen after rapamycin intervention in mice. Conclusion The decrease of Tregs in the early stage of obesity may contribute to abnormal distribution of macrophage subtypes in visceral adipose.