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过氧化物酶体增殖物激活受体γ(PPARγ)配体罗格列酮可调节瘦小鼠和肥胖小鼠支气管肺泡灌洗中瘦素、脂联素及炎性细胞因子的水平。

The peroxisome proliferator activated receptor gamma (PPARgamma) ligand rosiglitazone modulates bronchoalveolar lavage levels of leptin, adiponectin, and inflammatory cytokines in lean and obese mice.

作者信息

Holguin Fernando, Rojas Mauricio, Hart C Michael

机构信息

Emory University and the Atlanta Veterans Affairs Medical Center, Atlanta, Georgia 30308, USA.

出版信息

Lung. 2007 Dec;185(6):367-72. doi: 10.1007/s00408-007-9035-9. Epub 2007 Oct 2.

Abstract

Obese mice that lack leptin receptor (db (-) /db (-)) have been shown to have innate bronchial hyperresponsiveness (BHR). It has been proposed that the obesity-mediated BHR may involve a combination of increased leptin and reduced systemic adiponectin levels. The aim of this study was to determine if obesity modifies the airway concentration of leptin and adiponectin and whether treatment with a synthetic peroxisome proliferator-activated receptor gamma (PPARgamma) ligand can reduce airway leptin and increase airway adiponectin. In this study, obese, leptin receptor-deficient (db (-) /db (-)), or lean (db ( + ) /db (-)) mice were treated with rosiglitazone (3 mg/kg/day) or vehicle by gavage daily for 1 week. Bronchioalveolar lavage (BAL) was subsequently performed to determine levels of leptin, adiponectin, and inflammatory cytokines. Treatment with rosiglitazone increased BAL adiponectin levels in lean (p = 0.04) and to a lesser extent in obese mice (p = 0.07). Rosiglitazone treatment lowered leptin levels in lean mice, but increased leptin levels in BAL fluid of obese mice (p < 0.01). The BAL levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were lower in the lean rosiglitazone-treated group compared with the obese vehicle-treated group and lower in the obese rosiglitazone-treated group compared with the obese vehicle-treated group. These results demonstrate that obesity is associated with alterations in adipokine and cytokine levels in the airways that can be modulated by treatment with roziglitazone.

摘要

已证明缺乏瘦素受体的肥胖小鼠(db(-)/db(-))具有先天性支气管高反应性(BHR)。有人提出,肥胖介导的BHR可能涉及瘦素增加和全身脂联素水平降低的共同作用。本研究的目的是确定肥胖是否会改变气道中瘦素和脂联素的浓度,以及用合成的过氧化物酶体增殖物激活受体γ(PPARγ)配体治疗是否能降低气道瘦素水平并增加气道脂联素水平。在本研究中,肥胖、瘦素受体缺陷(db(-)/db(-))或瘦型(db(+)/db(-))小鼠每天通过灌胃给予罗格列酮(3mg/kg/天)或赋形剂,持续1周。随后进行支气管肺泡灌洗(BAL)以测定瘦素、脂联素和炎性细胞因子的水平。罗格列酮治疗使瘦型小鼠的BAL脂联素水平升高(p=0.04),在肥胖小鼠中升高程度较小(p=0.07)。罗格列酮治疗降低了瘦型小鼠的瘦素水平,但增加了肥胖小鼠BAL液中的瘦素水平(p<0.01)。与肥胖赋形剂治疗组相比,瘦型罗格列酮治疗组的粒细胞-巨噬细胞集落刺激因子(GM-CSF)的BAL水平较低,与肥胖赋形剂治疗组相比,肥胖罗格列酮治疗组的GM-CSF的BAL水平也较低。这些结果表明,肥胖与气道中脂肪因子和细胞因子水平的改变有关,而罗格列酮治疗可对其进行调节。

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