Department of Respiratory Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China.
Chin Med J (Engl). 2011 Aug;124(16):2502-6.
It is widely accepted that tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis of emphysema. This study aimed at investigating the protective effects of anti-TNF-α antibody, infliximab, in the development of emphysema induced by passive smoking in rats.
Thirty-nine rats were randomly divided into a normal control group (group 1), an emphysema group (group 2), and an infliximab-intervention group (group 3). Rat models of emphysema were established by exposure to cigarette smoking daily for 74 days. After 1 month, the infliximab intervention group was treated with infliximab via subcutaneous injection. The levels of TNF-α, IL-8 and vascular endothelial growth factor (VEGF) in bronchoalveolar lavage fluid (BALF) were measured with enzyme linked immunosorbent assay (ELISA). The number and classification of cells in the BALF were measured. Lung tissue sections stained by hematoxylin and eosin (HE) were observed, and mean linear intercept (MLI) and mean alveolar numbers (MAN) were measured. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) methods were used to examine the percentage of positive cells and distribution of apoptotic cells.
The levels of TNF-α and IL-8 in BALF were higher in group 2 than in group 1 and group 3. The MLI was greater in group 2 than that in group 1 and group 3 while MAN was decreased. The concentration of VEGF in BALF of group 2 was significantly decreased as compared with group 1. The total cells and neutrophils number was significantly increased in group 2 as compared with group 1 and group 3, so was the percentage of neutrophils. The number of TUNEL positive cells in the alveolar septa was significantly increased in group 2 as compared with group 1 and group 3.
Infliximab protects against cigarette smoking-induced emphysema by reducing airway inflammation, attenuating alveolar septa cell apoptosis and improving pathological changes.
肿瘤坏死因子-α（TNF-α）在肺气肿的发病机制中起着重要作用，这一观点已被广泛接受。本研究旨在探讨抗 TNF-α 抗体英夫利昔单抗（infliximab）对被动吸烟诱导的大鼠肺气肿发展的保护作用。
39 只大鼠随机分为正常对照组（第 1 组）、肺气肿组（第 2 组）和英夫利昔单抗干预组（第 3 组）。通过每日吸烟暴露 74 天建立大鼠肺气肿模型。1 个月后，英夫利昔单抗干预组通过皮下注射英夫利昔单抗进行干预。酶联免疫吸附试验（ELISA）测定支气管肺泡灌洗液（BALF）中 TNF-α、IL-8 和血管内皮生长因子（VEGF）的水平。测定 BALF 中细胞的数量和分类。苏木精和伊红（HE）染色肺组织切片，测量平均线性截距（MLI）和平均肺泡数（MAN）。末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）法检测阳性细胞百分比和凋亡细胞分布。
第 2 组 BALF 中 TNF-α 和 IL-8 水平高于第 1 组和第 3 组。第 2 组 MLI 大于第 1 组和第 3 组，而 MAN 降低。第 2 组 BALF 中 VEGF 浓度明显低于第 1 组。第 2 组总细胞和中性粒细胞数量明显高于第 1 组和第 3 组，中性粒细胞百分比也明显高于第 1 组和第 3 组。第 2 组肺泡隔中 TUNEL 阳性细胞数明显多于第 1 组和第 3 组。
英夫利昔单抗通过减轻气道炎症、减轻肺泡隔细胞凋亡和改善病理变化，对吸烟诱导的肺气肿具有保护作用。
