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过氧化物酶体增殖物激活受体(PPAR)-α和PPAR-γ在肥胖小鼠肺组织中的表达及罗格列酮对肺组织中促炎细胞因子表达的影响

Expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ in the lung tissue of obese mice and the effect of rosiglitazone on proinflammatory cytokine expressions in the lung tissue.

作者信息

Ryu Seung Lok, Shim Jae Won, Kim Duk Soo, Jung Hye Lim, Park Moon Soo, Park Soo-Hee, Lee Jinmi, Lee Won-Young, Shim Jung Yeon

机构信息

Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Korean J Pediatr. 2013 Apr;56(4):151-8. doi: 10.3345/kjp.2013.56.4.151. Epub 2013 Apr 22.

Abstract

PURPOSE

We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-γ agonist.

METHODS

We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, PPAR-α and PPAR-γ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid.

RESULTS

Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPARα and PPAR-γ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-α, and TGF-β mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-β expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid.

CONCLUSION

PPAR-α and PPAR-γ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.

摘要

目的

我们研究了在有无卵清蛋白(OVA)激发的情况下,瘦小鼠和肥胖小鼠肺组织中过氧化物酶体增殖物激活受体(PPAR)-α、PPAR-γ、脂肪因子和细胞因子的mRNA水平,以及PPAR-γ激动剂罗格列酮的作用。

方法

我们建立了6种小鼠模型:接受OVA激发且使用或未使用罗格列酮的瘦小鼠;使用或未使用罗格列酮的肥胖小鼠;接受OVA激发且使用或未使用罗格列酮的肥胖小鼠。我们对肺组织中的瘦素、瘦素受体、脂联素、血管内皮生长因子(VEGF)、肿瘤坏死因子(TNF)-α、转化生长因子(TGF)-β、PPAR-α和PPAR-γ进行实时聚合酶链反应,并测定支气管肺泡灌洗液中的细胞计数和细胞因子水平。

结果

接受OVA激发的小鼠表现出气道高反应性。与其他类型的小鼠相比,接受OVA激发的肥胖小鼠肺组织中PPARα和PPAR-γ的mRNA水平显著升高,而在给予罗格列酮后降低。在有无OVA激发的肥胖小鼠中,瘦素和瘦素受体表达均增加,而在罗格列酮治疗后降低。接受OVA激发的瘦小鼠中脂联素mRNA水平升高。与对照小鼠相比,有无OVA激发的肥胖小鼠肺组织中VEGF、TNF-α和TGF-β的mRNA水平均升高。然而,罗格列酮仅降低了肥胖小鼠中TGF-β的表达,甚至在所有类型的小鼠中均增强了VEGF的表达。罗格列酮治疗并未降低气道反应性,但增加了支气管肺泡灌洗液中的中性粒细胞和巨噬细胞。

结论

在接受OVA激发的肥胖小鼠肺组织中,PPAR-α和PPAR-γ表达上调,然而,罗格列酮治疗并未下调这些小鼠的气道炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c41/3641311/c1f07dc63db7/kjped-56-151-g001.jpg

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