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[白细胞介素-17抗体对双酚A诱导的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].

作者信息

Lu Xiaotong, Luo Shimeng, Li Hanqin, Zhang Xiaofei, Wu Ming, Du Zhiyuan, Zhu Qixing, Shen Tong

机构信息

Department of Occupational and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, China.

出版信息

Wei Sheng Yan Jiu. 2018 Nov;47(6):949-955.

Abstract

OBJECTIVE

To study the effects of IL-17 antibody on adipose tissue inflammation and macrophage accumulation in obese mice induced by BPA.

METHODS

4-week-old male C57 BL/6 mice were fed with high fat diet( HFD) and were randomly divided into solvent control group, IgG treatment group, IL-17 antibody treatment group, 1000 nmol/L BPA group, IgG + 1000 nmol/L BPA group, IL-17 antibody + 1000 nmol/L BPA group, with 8 mice in each group. The BPA exposed group administered 1000 nmol/L BPA by drinking water. The mice in IL-17 treatment group were intraperitoneally injected with 100 μg IL-17 antibody and the mice in IgG treatment group were intraperitoneally injected with 100 μg IgG each week. Mice were sacrificed and epididymal fat pad was obtained after 16 weeks. Histopathological section was used to observe the cells morphological changes and inflammation in epididymal adipose tissue. Immunohistochemistry( IHC) was used to detect the expression of IL-17、TNF-α and IL-1β in epididymal adipose tissue. Immunofluorescence( IF) was used to detect the location of macrophage 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. 81) g]of mice in 1000 nmol/L BPA group higher than the mice in solvent control group( body weight [( 38. 44 ± 4. 23) g], the obesity rate [( 28. 90 ± 14. 19) % ]), the difference was statistically 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 upregulated. And the macrophage accumulation was increased( F = 90. 829, P < 0. 05). Compared with the 1000 nmol/L BPA group, IgG treatment groups( the obesity rate[( 35. 98 ± 10. 73) % ]) had less effect on the mice. IL-17 treatment( the obesity rate[( 23. 03 ± 12. 50) % ]) inhibited BPA-induced increased in obesity rate of mice. Also, the inflammatory infiltration and macrophage accumulation 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, P < 0. 05) inflammatory factors were decreased.

CONCLUSION

IL-17 antibody can improve BPA-induced mice obesity by reducing adipose tissue macrophage accumulation and reducing adipose tissue inflammation.

摘要

目的

研究白细胞介素-17(IL-17)抗体对双酚A(BPA)诱导的肥胖小鼠脂肪组织炎症和巨噬细胞聚集的影响。

方法

4周龄雄性C57 BL/6小鼠喂食高脂饮食(HFD),随机分为溶剂对照组、IgG治疗组、IL-17抗体治疗组、1000 nmol/L BPA组、IgG + 1000 nmol/L BPA组、IL-17抗体 + 1000 nmol/L BPA组,每组8只小鼠。BPA暴露组通过饮水给予1000 nmol/L BPA。IL-17治疗组小鼠每周腹腔注射100 μg IL-17抗体,IgG治疗组小鼠每周腹腔注射100 μg IgG。16周后处死小鼠,获取附睾脂肪垫。采用组织病理学切片观察附睾脂肪组织中细胞形态变化和炎症情况。采用免疫组织化学(IHC)检测附睾脂肪组织中IL-17、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的表达。采用免疫荧光(IF)检测附睾脂肪组织中巨噬细胞的定位。采用单因素方差分析比较两组均值,采用Tukey法进行两两比较。

结果

1000 nmol/L BPA组小鼠的肥胖率[(40.68±9.43)%]和体重[(41.95±2.81)g]高于溶剂对照组小鼠(体重[(38.44±4.23)g],肥胖率[(28.90±14.19)%]),差异具有统计学意义(体重F = 5.895,P < 0.05,肥胖率F = 5.895,P < 0.05)。附睾脂肪组织炎性细胞浸润增加。IL-17(F = 28.225,P < 0.05)和IL-1β(F = 57.878,P < 0.05)的表达上调。并且巨噬细胞聚集增加(F = 90.829,P < 0.05)。与1000 nmol/L BPA组相比,IgG治疗组(肥胖率[(35.98±10.73)%])对小鼠的影响较小。IL-17治疗(肥胖率[(23.03±12.50)%])抑制了BPA诱导的小鼠肥胖率增加。此外,脂肪组织的炎性浸润和巨噬细胞聚集减少(F = 90.829,P < 0.05)。并且IL-17(F = 28.225,P < 0.05)、TNF-α(F = 4.199,P < 0.05)和IL-1β(F = 57.878,P < 0.05)炎性因子的表达降低。

结论

IL-17抗体可通过减少脂肪组织巨噬细胞聚集和减轻脂肪组织炎症来改善BPA诱导的小鼠肥胖。

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