白细胞介素-17抗体对双酚A诱导肥胖小鼠脂肪组织炎症的影响

Effects of IL-17 antibody on inflammation of adipose tissue in obese mice induced by bisphenol A

目的探究白细胞介素(IL)-17抗体对双酚A(BPA)诱导的肥胖小鼠脂肪组织炎症以及巨噬细胞聚集的影响。方法 4周龄雄性C57BL/6小鼠随机分为溶剂对照组、免疫球蛋白(Ig) G同型对照组、IL-17抗体组、1000 nmol/L BPA组、IgG+1000 nmol/L BPA组、IL-17抗体+1000 nmol/L BPA组,每组8只,高脂饲料(HFD)喂养,经饮水摄入BPA; IgG同型对照组和IgG+1000 nmol/L BPA组每周腹腔注射IgG抗体100μg,IL-17抗体组和IL-17抗体+1000 nmol/L BPA组每周腹腔注射IL-17抗体100μg。暴露16周时处死小鼠,取附睾脂肪垫,HE染色观察脂肪组织病理学改变,免疫组化(IHC)检测脂肪组织IL-17、肿瘤坏死因子(TNF)-α和IL-1β的表达,免疫荧光(IF)检测脂肪组织中巨噬细胞的聚集。组间均值比较采用单因素方差分析(One-Way ANOVA),用Tukey法进行两两比较。结果 1000 nmol/L BPA组小鼠体重[(41. 95±2. 81) g]和肥胖率[(40. 68±9. 43)%]均高于溶剂对照组([体重(38. 44±4. 23) g],肥胖率[(28. 90±14. 19)%]),差异有统计学意义(体重F=5. 895,P <0. 05;肥胖率F=5. 895,P <0. 05)。1000 nmol/L BPA组小鼠附睾脂肪组织炎性细胞浸润较对照组显著增多,IL-17 (F=28. 225,P <0. 05)和IL-1β(F=57. 878,P <0. 05)的表达上调,脂肪组织中巨噬细胞聚集增加(F=90. 829,P <0. 05)。与1000 nmol/L BPA组相比,IgG同型对照组小鼠肥胖率[(35. 98±10. 73)%]、脂肪组织炎症及巨噬细胞聚集差异不显著,而IL-17抗体组小鼠肥胖率[(23. 03±12. 50)%]下降,脂肪组织炎性细胞浸润减少,炎性因子IL-17 (F=28. 225,P <0. 05)、TNF-α(F=4. 199,P <0. 05)、IL-1β(F=57. 878,P <0. 05)的表达下调,巨噬细胞聚集减少(F=90. 829,P <0. 05)。结论 IL-17抗体可通过减少脂肪组织巨噬细胞的聚集,减轻脂肪组织炎症,从而改善BPA诱导的小鼠肥胖。

Objective Fo study lhe effects of 11-17 antibody on adipose tissue inflammation and macrophage aeeumulation in obese mice induced by BPA.Methods 4-week-old male C57BL/6 mice were fed with high fat diet(HFD)and were randomly divided into solvent eontrol group,IgG treatment group,IL-17 antilmdy treatment group,1000 nmol/1 BPA group.IgG+1000nmol/L BPA group,IL-17 antibody+1000 nmol/L BPA group,with 8 mice in each group.The BPA exposed group administered 1000 nnml/I BPA by drinking water. The mice in IL-17 treatment group were intraperitoneally injected with 100 txg IL一1 7 antibo<ty and the mice in IgG treatment group wereintraperitoneally injected with 1 00 μg IgG each week. Mice were sacrificed and epididymal fat pad was ohtained after 16 weeks. Histopathological section was used to observe the cells morphological changes and inflamnmtion in epididymal adipose tissue.Immunohistoehemistry(IHC)was used to detect the expression of II -17、TNF-α and IL-1β in epididymal adipose tissue.Immunofluorescenee(IF)was used to detect the loeation of maerophage in the epididymal adipose tissue. One-Way ANOVA was used to compare the mean values of the two groups, and the Tukey method was used for pairwise comparison.Results The obesity rate[(40.68±9.43)%]and body weight[(41.95±2.8 1)g] of mice in 1 000 nmol/L BPA group higher than the nliee in solvent control group(body weight[(38.44±4.23)g],the obesity rate[(28.90±14.19)% ]),the difference was statistieally significant(body weight F=5.895,P<0.05,the obesity rate F =5.895.P <0.05).Epididymal adipose tissue inflammatory cell infiltration increased.The expression of IL-17(F=28.225,P<0.05)and IL-1β(F=57.878,P<0.05)were upregulate)t.And the macrophage aceunmlation was increased(F =90.829,P <0.05).Compared with the 1 000 nmol/L BPA group,IgG treatment groups (the obesity rate[(35.98±10.73)%])had less efect on the mice.IL-17 treatment(the obesity rate[(23.03±12.50)% ])inhibited BPA-induced increased in obesity rate of nlice.Also,the inflammatory infihralion and macrophage aecunm lation of the adipose tissue were reduced(F=90.829,P<0.05).And the expression of IL-17(F=28.225,P<0.05),TNF-α(F=4.199,P<0.05)and IL-1β(F=57.878,JD<0.05)inflammatory faetorswere decreased. Conclusion IL-17 antihody can improve BPA-induced mice obesity by reducing adipose tissue macrophage aceunm lation and reducing adipose tissue inflammation.