Etanercept attenuates short-term cigarette-smoke-exposure-induced pulmonary arterial remodelling in rats by suppressing the activation of TNF-伪/NF-魏B signal and the activities of MMP-2 and MMP-9

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• 作者：Hong Xue^a ; ^{hong_xue1987@yahoo.com.cn} ; Kai Sun^a ; ^{sunkai@njmu.edu.cn} ; Weiping Xie^a ; ^{wpxie@yahoo.com} ; Gang Hu^b ; Hui Kong^a ; Qiang Wang^a ; ^{qiangwang@126.net} ; Hong Wang^a ; ^{wanghong_njmu@yahoo.com}
• 关键词：Pulmonary arterial remodelling ; Cigarette-smoke-exposure ; Etanercept ; Tumour necrosis factor-alpha ; Matrix metalloproteinase ; Nuclear factor-kappa B(NF-kappa B)
• 刊名：Pulmonary Pharmacology & Therapeutics
• 出版年：2012
• 期刊代码：56_10945539
• 类别：pha
• 出版时间：June, 2012
• 卷：25
• 期：3
• 页码：208-215
• 文件大小：839 K

摘要

The pathogenesis of cigarette-smoke-exposure-induced pulmonary vasculature impairment is unclear. Cigarette-smoke-exposure-induced the accumulation of tumour necrosis factor-alpha (TNF-伪) and up-regulates the expression and activities of matrix metalloproteinases (MMPs) involved in smoke-induced vascular remodelling, which are important processes in the pathogenesis of vasculature impairment. The TNF-伪 antagonist Etanercept is an anti-inflammatory drug with a potential role in regulating MMP expression. To determine the effect of Etanercept on short-term smoke-induced pulmonary arteriole impairment and investigate its possible mechanism, male Sprague-Dawley rats were exposed to cigarette-smoke daily for two weeks in both the absence and presence of Etanercept. Cigarette-smoke-exposure-induced elevation of mean pulmonary artery pressures and medial hypertrophy of pulmonary arterioles were partially reduced by Etanercept. Up-regulation of the expression and activities of MMP-2 and MMP-9, induced by cigarette-smoke, were also suppressed significantly by Etanercept. Furthermore, Etanercept treatment significantly attenuated cigarette-smoke-induced TNF-伪 accumulation and activation of nuclear factor NF-魏B signal. These results suggest that Etanercept have the protective effects in cigarette-smoke-induced pulmonary vascular remodelling, with the attenuation of the up-regulated expression and activities of MMP-2 and MMP-9 and activation of TNF-伪/NF-魏B signal pathway probably being involved as part of its mechanism. Our study might provide insight into the development of new interventions for vasculature impairment.