Valença Samuel Santos, Porto Luís Cristóvão
Departamento de Histologia e Embriologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
J Bras Pneumol. 2008 Oct;34(10):787-95. doi: 10.1590/s1806-37132008001000006.
Various studies of emphysema involve long-term exposure of animals to cigarette smoke, focusing on the cell type involved in the protease/antiprotease imbalance and on extracellular matrix degradation. In emphysema, increased expression of metalloproteinases is associated with cytokines, and evidence suggests that the matrix metalloproteinase-12 (MMP-12) plays an important role. Our objective was to investigate tissue inhibitor of metalloproteinase-2 (TIMP-2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) detection by immunohistochemical methods in mouse lung.
Male C57BL/6 mice were exposed 3 times a day to smoke of 3 cigarettes over a period of 10, 20, 30 or 60 days in an inhalation chamber (groups CS10, CS20, CS30 and CS60, respectively). Controls were exposed to the same conditions in room air.
A progressive increase in the number of alveolar macrophages was observed in the bronchoalveolar lavage fluid of the exposed mice. The mean linear intercept, an indicator of alveolar destruction, was greater in all exposed groups when compared to control group. In the CS10, CS20 and CS30 mice, the immunohistochemical index (II) for MMP-12 increased in parallel with a decrease in II for TIMP-2 in the CS10, CS20 and CS30 mice. The II for the cytokines TNF-alpha and IL-6 was greater in all exposed groups than in the control group. Emphysema, with changes in volume density of collagen and elastic fibers, was observed in the CS60 group.
These findings suggest that cigarette smoke induces emphysema with major participation of TNF-alpha and IL-6 without participation of neutrophils.
多项肺气肿研究涉及让动物长期暴露于香烟烟雾中，重点关注参与蛋白酶/抗蛋白酶失衡的细胞类型以及细胞外基质降解。在肺气肿中，金属蛋白酶表达增加与细胞因子有关，且有证据表明基质金属蛋白酶-12（MMP-12）起重要作用。我们的目的是通过免疫组化方法检测小鼠肺组织中金属蛋白酶组织抑制剂-2（TIMP-2）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）。
雄性C57BL/6小鼠在吸入舱中每天暴露于3支香烟的烟雾3次，持续10、20、30或60天（分别为CS10、CS20、CS30和CS60组）。对照组在相同条件下暴露于室内空气。
在暴露小鼠的支气管肺泡灌洗液中观察到肺泡巨噬细胞数量逐渐增加。与对照组相比，所有暴露组的平均线性截距（肺泡破坏的指标）更大。在CS10、CS20和CS30小鼠中，MMP-12的免疫组化指数（II）升高，同时TIMP-2的II降低。所有暴露组中细胞因子TNF-α和IL-6的II均高于对照组。在CS60组中观察到肺气肿，伴有胶原纤维和弹性纤维体积密度的变化。
这些发现表明，香烟烟雾诱导肺气肿，主要由TNF-α和IL-6参与，而中性粒细胞未参与。
