The PPAR gamma agonist, rosiglitazone, attenuates airway inflammation and remodeling via heme oxygenase-1 in murine model of asthma
The PPAR gamma agonist, rosiglitazone, attenuates airway inflammation and remodeling via heme oxygenase-1 in murine model of asthma
复制标题
PPAR γ 激动剂罗格列酮通过血红素氧合酶 1 在哮喘小鼠模型中减轻气道炎症和重塑
DOI：
10.1038/aps.2014.128
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发表时间：
2015
影响因子：
8.2
通讯作者：
Li MX
中科院分区：
文献类型：
--
作者：
Xu Jing;Zhu Yan-ting;Wang Gui-zuo;Han Dong;Wu Yuan-yuan;Zhang Xin;Liu Yun;Zhang Yong-hong;Xie Xin-ming;Li Shao-jun;Lu Jia-mei;Liu Lu;Feng Wei;Sun Xiu-zhen;Li Man-xiang;Li MX
目的：罗格列酮是一种特异性的过氧化物酶体增殖物激活受体γ激动剂，对哮喘有潜在的治疗作用。虽然认为PPARγ激活在抑制哮喘气道炎症和重塑中具有保护作用，但其具体机制尚不清楚。本研究旨在探讨血红素氧合酶-1（HO-1）相关通路是否参与罗格列酮激活的过氧化物酶体增殖物激活受体γ（PPARγ）信号通路在哮喘治疗中的作用。在每次OVA攻击之前，小鼠接受罗格列酮（5 mg/kg，po）。处死小鼠后，收集支气管肺泡灌洗液（BALF）、血液样品和肺用于分析。结果：罗格列酮能明显减轻哮喘小鼠气道炎症和重塑，表现为BALF中细胞总数、嗜酸性粒细胞和中性粒细胞计数减少，IL-5和IL-13水平降低，气道平滑肌层厚度减少，气道胶原沉积减少。罗格列酮还能显著增加气道组织中过氧化物酶体增殖物激活受体γ（PPARγ）、血红素氧合酶（HO-1）和p21蛋白的表达，降低基质金属蛋白酶（MMP-2）和基质金属蛋白酶（MMP-9）的活性，增加HO-1的活性。结论：罗格列酮通过激活PPARγ/HO-1信号通路，有效减轻哮喘小鼠气道炎症和重塑。
Aim:Rosiglitazone is one of the specific PPARγ agonists showing potential therapeutic effects in asthma. Though PPARγ activation was considered protective in inhibiting airway inflammation and remodeling in asthma, the specific mechanisms are still unclear. This study was aimed to investigate whether heme oxygenase-1 (HO-1) related pathways were involved in rosiglitazone-activated PPARγ signaling in asthma treatment.Methods:Asthma was induced in mice by multiple exposures to ovalbumin (OVA) in 8 weeks. Prior to every OVA challenge, the mice received rosiglitazone (5 mg/kg, po). After the mice were sacrificed, the bronchoalveolar lavage fluid (BALF), blood samples and lungs were collected for analyses. The activities of HO-1, MMP-2 and MMP-9 in airway tissue were assessed, and the expression of PPARγ, HO-1 and p21 proteins was also examined.Results:Rosiglitazone administration significantly attenuated airway inflammation and remodeling in mice with OVA-induced asthma, which were evidenced by decreased counts of total cells, eosinophils and neutrophils, and decreased levels of IL-5 and IL-13 in BALF, and by decreased airway smooth muscle layer thickness and reduced airway collagen deposition. Furthermore, rosiglitazone administration significantly increased PPARγ, HO-1 and p21 expression and HO-1 activity, decreased MMP-2 and MMP-9 activities in airway tissue. All the therapeutic effects of rosiglitazone were significantly impaired by co-administration of the HO-1 inhibitor ZnPP.Conclusion:Rosiglitazone effectively attenuates airway inflammation and remodeling in OVA-induced asthma of mice by activating PPARγ/HO-1 signaling pathway.