Inhibition of tumor necrosis factor-a reduces alveolar septal cell apoptosis in passive smoking rats
Inhibition of tumor necrosis factor-a reduces alveolar septal cell apoptosis in passive smoking rats
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DOI：
10.1097/00029330-200804010-00005
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发表时间：
2008-04-05
影响因子：
6.1
通讯作者：
Zhou Rui
中科院分区：
文献类型：
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作者：
Zhang Cheng;Cai Shan;Zhou Rui
背景最近的研究表明，肺细胞凋亡在香烟诱发的慢性阻塞性肺病（COPD）的发病机制中发挥着重要作用。肿瘤坏死因子α（TNF-α）是慢性阻塞性肺病（COPD）中最重要的细胞因子之一。本研究旨在探讨其抑制剂重组人坏死因子α受体II:IgG Fc融合蛋白(rhTNFR:Fc)对被动吸烟大鼠肺泡间隔细胞凋亡的影响。方法将48只大鼠随机分为正常对照组、被动吸烟组、rhTNFR:Fc干预组和假手术干预组。被动吸烟大鼠接受每天吸烟80天的治疗。吸烟1个月后rhTNFR:Fc干预组皮下注射rhTNFR:Fc,假手术干预组皮下注射中性制剂(生理盐水0.1 ml、甘露醇0.8 ml、蔗糖0.2 mg、Tris 0.024 mg作为对照)。测定肺功能并测定血清和支气管肺泡灌洗液(BALF)中TNF-α的水平采用酶联免疫吸附试验（ELISA）观察肺组织切片的形态学变化，测量平均线性截距（MLI）和平均肺泡数（MAN），并进行末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）法测定阳性细胞百分比和凋亡细胞分布。与正常对照组和rhTNFR:Fc干预组相比，被动吸烟组均发现MAN（P
Background Recent studies have revealed that lung cell apoptosis plays an important role in pathogenesis of cigarette-induced chronic obstructive pulmonary disease (COPD). Tumor necrosis factor alpha (TNF-alpha) is one of the most important cytokines which are involved in COPD. This study aimed at investigating the influence of its inhibitor, recombinant human necrosis factor-alpha receptor II:IgG Fc fusion protein (rhTNFR:Fc) on alveolar septal cell apoptosis in passive smoking rats.Methods Forty-eight rats were randomly divided into a normal control group, a passive smoking group, an rhTNFR:Fc intervention group and a sham intervention group. The passive smoking rats were treated by exposure to cigarette smoking daily for 80 days. After smoking for one month the rhTNFR:Fc intervention group was treated with rhTNFR:Fc by subcutaneous injection, the sham intervention group injected subcutaneously with a neutral preparation (normal saline 0.1 ml, manicol 0.8 ml, cane sugar 0.2 mg, Tris 0.024 mg as a control. Lung function was determined and the levels of TNF-alpha in serum and broncho-alveolar lavage fluid (BALF) were measured with enzyme-linked immunosorbnent assay (ELISA). Lung tissue sections stained by hematoxylin and eosin (HE) were observed for study of morphological alternations. Mean linear intercept (MLI) and mean alveolar numbers (MAN) were measured and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was carried out to determine the percentage of positive cells and distribution of apoptotic cells.Results Increased MLI and decreased MAN were found in the passive smoking group compared with both the normal control group and the rhTNFR:Fc intervention group (P