[A comparative study of two chronic obstructive pulmonary disease mouse models established by different methods].

Objective: To compare chronic obstructive pulmonary disease (COPD) mouse models established by two different methods-cigarette smoke (CS) exposure alone and CS exposure combined with airway instillation of bacterial LPS. Methods: Male C57 mice were randomly divided into control group(CTL group), CS exposure group (CS group) and intra-tracheal LPS instillation combined with CS exposure group (LPS+CS group) according to the random number table, with 8 rats in each group. After the models were established, we measured the lung function and collected the bronchoalveolar lavage fluid (BALF) to detect the number of inflammatory cells and the expression of mucin and inflammatory mediators. HE and PAS staining were performed to observe the pathological changes in airway and lung tissue and to detect the goblet cells in airway, respectively. Results: Total lung capacity (TLC), functional residual capacity (FRC) and airway resistance (RI) of the CS and LPS+CS groups were higher than those of the CTL group, while the FEV(50)/FVC of these 2 groups was lower (P<0.05). Moreover, both RI and FEV(50)/FVC in the LPS+CS group were higher compared with the CS group (P<0.05). HE staining of lung tissue showed that the average alveolar intercept and thickness of small airway wall in the CS and LPS+CS groups were higher compared to the CTL group. In addition, the average alveolar intercept in the LPS+CS group was lower than that in the CS group [(47.86±2.82) µm and (61.94±7.68) µm respectively, P<0.05], but the area of bronchial inflammation of LPS+CS group was higher. The number of total white blood cells, neutrophils, lymphocytes, macrophages and the level of interleukin-6 (IL-6) in BALF of CS and LPS+CS groups were higher than those of CTL group (all P<0.05). Furthermore, the number of neutrophils and IL-6 level in BALF of LPS+CS group were higher in comparison with CS group, while the number of macrophages in BALF of LPS+CS group was lower (P<0.05). PAS staining of lung tissue indicated that the number of goblet cells in large airways of CS and LPS+CS groups increased more significantly compared to the CTL group, and the number of goblet cells in the LPS+CS group was higher than that in the CS group [(0.16±0.02) and (0.09±0.02) respectively, P<0.05]. The expression levels of Muc5ac and Muc5b in BALF of LPS+CS and CS groups were also higher than those of CTL group (P<0.05), and the level of Muc5ac in BALF of LPS+CS group was higher compared with CS group[(2.69±0.72) and (2.19±0.29) respectively, P<0.05]. Conclusions: Combined exposure of LPS and CS for establishing a COPD mouse model could better simulate the pathological characteristics of human COPD during the acute exacerbation period. The COPD mouse model established by CS exposure alone was able to better imitate the basic features of human COPD in the stable period. Researchers could choose a more appropriate modeling method according to different purposes.

Expression of adhesion molecules and mucins in human and rhesus macaque gastrointestinal epithelial cells.

Epithelial junctions and mucins play key roles in the gastrointestinal mucosal barrier, and their alterations are associated with numerous diseases, including carcinomas. The systematic expression of adhesion molecules and mucins in normal and malignant human gastrointestinal cells was investigated in this study. In normal human gastrointestinal cells, zonula occludens-1 (ZO-1), α-catenin, ß-catenin, γ-catenin and desmoglein-2 (DSG2) were located in the cytoplasmic membranes, whereas symplekin stained in the nuclei. ZO-1, the three catenins, and DSG2 were observed in the gastric and colorectal carcinomas with reduced and heterogeneous expression and with abnormal distribution. Symplekin was detected in the nuclei of tumor cells in most tumors but not observed in some others. The immunohistochemical results for ZO-1 and symplekin on the tissues were consistent with the data for the cultured cells obtained by immunocytochemical staining and Western blot analysis. MUC1 was not stained in the normal gastrointestinal cells without periodate oxidation, but it was strongly labeled in the malignant gastrointestinal cells. MUC2 was detected in the normal and malignant gastrointestinal cells without the periodate treatment. These findings indicate that alterations in the expression of the epithelial junctions and mucins are associated with the malignant transformation of gastrointestinal cells. In addition, the gastrointestinal epithelial cells of rhesus macaques expressed these adhesion molecules and mucins, as did the human cells, suggesting that the rhesus monkey is a suitable experimental animal model for research on adhesion molecules and mucins.