Protective effect of adiponectin on paraquat-induced pulmonary fibrosis in mice

Protective effect of adiponectin on paraquat-induced pulmonary fibrosis in mice
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脂联素对百草枯所致小鼠肺纤维化的保护作用

DOI:
10.1007/s13273-015-0024-4
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发表时间:
2015-07
影响因子:
1.7
通讯作者:
Yu Cao
Yu Cao
中科院分区:
医学4区
文献类型:
--
作者:
Rong Yao;Yarong He;Zhi Zeng;Zongan Liang;Yu Cao

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肺纤维化(PF)是百草枯(PQ)中毒最常见的并发症,缺乏有效的治疗方法。本研究旨在探讨外源性脂联素(APN)亚型是否对PQ诱导的PF具有保护作用,并研究这些作用的可能机制。将80只BALB/C小鼠随机分为对照组、PQ组、APN低剂量组和APN高剂量组。将人肺WI-38成纤维细胞类似地分为对照组、PQ组和APN组,并在PQ暴露后24 h、48 h和72 h进行检查。采用HE染色和Masson三色染色观察小鼠肺组织病理学变化。采用Western blot和实时荧光定量PCR(RT-PCR)方法检测小鼠肺组织转化生长因子β1(TGF-β1)蛋白和mRNA的表达,以及肺成纤维细胞α-SMA、III型胶原和NF-κB p65的表达。使用二氢乙锭(DHE)检测成纤维细胞中的细胞内超氧阴离子(O2−)。APN能明显减轻PQ诱导的肺纤维化,并呈剂量依赖性降低肺组织TGF-β 1蛋白和mRNA表达水平(P<0.05)。当成纤维细胞用APN预处理时,α-SMA和NF-κB p65的表达下调,O2−减少。PQ暴露后,抗炎因子IL-1 Ra的表达上调(P<0.05)。本研究揭示了其可能通过抑制NF-κB依赖的炎症和TGF-β 1介导的纤维化事件而发生。
Pulmonary fibrosis (PF) is the most common complication of paraquat (PQ) toxicity, which lacks an effective treatment. This study aimed to investigate whether exogenous administration of globular adiponectin (APN) isoform provided protection against PQ-induced PF, and examined the possible mechanisms underlying these effects. Eighty BALB/C mice were randomly divided into control, PQ, low-dose APN, and high-dose APN groups. Human lung WI-38 fibroblasts were similarly divided into control, PQ, and APN groups and examined at 24 h, 48 h, and 72 h after PQ exposure. Hematoxylin and eosin (HE) and Masson trichrome staining were used to compare the histopathologic changes in the mouse lung tissues. Western blot and real-time quantitative-PCR (RT-PCR) were used to measure the protein and mRNA expression of transforming growth factor β1(TGF-β1) in mice lung tissues and α-SMA, type III collagen, and NF-κB p65 in lung fibroblasts. Dihydroethidium (DHE) was used to detect intracellular superoxide anion (O2−) in fibroblasts. APN administration significantly ameliorated PQ-mediated fibrosis histologically and reduced the protein and mRNA expression levels of TGF-β1in mouse lung tissues in a dose-dependent manner (P<0.05). When fibroblasts were pretreated with APN, the expression of aα-SMA and NF-κB p65 were down-regulated, and O2−decreased. Expression of the anti-inflammatory factor IL-1Ra was upregulated following PQ exposure (P<0.05). This study revealed which may have occurred through suppression of NF-κB dependent inflammatory and TGF-β1mediated fibrotic events.
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