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肥胖大鼠循环和脾脏白细胞中整合素表达及过氧化氢生成

Integrin expression and H2O2 production in circulating and splenic leukocytes of obese rats.

作者信息

Kim Choong H, Vaziri Nosratola D, Rodriguez-Iturbe Bernardo

机构信息

Renal Service, Hospital Universitario, Avenida Goajira s/n, Maracaibo, Venezuela.

出版信息

Obesity (Silver Spring). 2007 Sep;15(9):2209-16. doi: 10.1038/oby.2007.262.

DOI:10.1038/oby.2007.262
PMID:17890488
Abstract

OBJECTIVE

Obesity is associated with oxidative stress and inflammation. We hypothesized that the pro-inflammatory state in obesity may result in spontaneous activation and, hence, increased generation of reactive oxygen species (ROS) and integrin expression in the circulating leukocytes.

METHODS

Flow cytometry was used to determine integrin expression (immunostaining) as well as superoxide and hydrogen peroxide productions (fluorescent probes) in the peripheral blood and splenic leukocyte of 24-week-old male obese normotensive and not-as-yet diabetic Zucker rats (n = 6) and their lean counterparts (n = 6).

RESULTS

Obese rats had hyperlipidemia and normal arterial pressure, plasma glucose, and creatinine concentrations. Nevertheless, obese rats exhibited increased hydrogen peroxide production by circulating and splenic CD4+ and CD8+ T lymphocytes and by splenic macrophages. This was accompanied by up-regulations of CD11a expression in the peripheral blood and splenic CD4+ T cells, CD11b in circulating macrophages, and CD11a and CD18 in circulating granulocytes.

CONCLUSION

The study revealed direct evidence of spontaneous leukocyte activation and increased ROS generation by T lymphocytes and monocytes in the peripheral blood of obese Zucker rats before the development of diabetes or hypertension. These findings illustrate the link between obesity, oxidative stress, and inflammation.

摘要

目的

肥胖与氧化应激和炎症相关。我们推测,肥胖中的促炎状态可能导致循环白细胞中活性氧(ROS)的自发激活及生成增加,以及整合素表达增加。

方法

采用流式细胞术测定24周龄雄性肥胖血压正常且尚未患糖尿病的 Zucker 大鼠(n = 6)及其瘦型对照大鼠(n = 6)外周血和脾脏白细胞中的整合素表达(免疫染色)以及超氧化物和过氧化氢生成(荧光探针)。

结果

肥胖大鼠存在高脂血症,动脉血压、血糖和肌酐浓度正常。然而,肥胖大鼠循环及脾脏中的 CD4⁺和 CD8⁺T 淋巴细胞以及脾脏巨噬细胞的过氧化氢生成增加。外周血和脾脏 CD4⁺T 细胞中的 CD11a 表达上调,循环巨噬细胞中的 CD11b 上调,循环粒细胞中的 CD11a 和 CD18 上调。

结论

该研究揭示了在糖尿病或高血压发生之前,肥胖 Zucker 大鼠外周血中 T 淋巴细胞和单核细胞自发白细胞激活及 ROS 生成增加的直接证据。这些发现阐明了肥胖、氧化应激和炎症之间的联系。

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