摘要
目的观察NOX4在博来霉素诱导的小鼠纤维化肺中的表达及其意义,探讨PFD对NOX4表达的影响。方法 72只C57健康雌性小鼠采用数字表法随机分为PFD干预组(A组)、模型组(B组)、正常对照组(C组)3组,每组各18只。采用气管内注入博来霉素(3.5mg/kg)的方法构建小鼠肺纤维化模型。小鼠肺组织行病理切片HE和Masson染色,检测肺组织羟脯氨酸(Hyp)含量,免疫组织化学方法检测NOX4在肺组织中的表达。结果 Masson染色显示:造模后B组于第7天、第14天、第28天3个时间点肺纤维化评分较C组均增加(P<0.05);A组肺纤维化评分较B组降低(P<0.05)。造模第7、14、28天3个时间点B组肺组织Hyp含量较C组均增高(P<0.05);A组肺组织Hyp含量较B组减低(P<0.05)。免疫组化显示造模第7、14、28天3个时间点B组小鼠肺组织均可见在气道平滑肌细胞、上皮细胞、肺泡上皮细胞,以及血管平滑肌细胞、内皮细胞,肺成纤维细胞中NOX4广泛的强表达;C组NOX4表达较B组弱(P<0.05);A组NOX4表达较B组减弱(P<0.05)。结论 NOX4在肺组织广泛表达,其表达上调可能与博来霉素诱导的肺纤维化形成相关。PFD可下调NOX4表达,提示NOX4有望成为治疗肺纤维化的新靶点。
Objective To observe the expression and role of NOX4 in the bleomycin（BLM） - induced pulmonary fibrosis in mice, and to investigate the effects of pirfenidone on the expression of NOX4. Methods Seventy - two female adult （C57BL/6） mice were randomly divided into four groups as the following（each group includes eighteen mice） ： the control group （Group C） , the bleomycin group （Group M）, the pirfenidone group（ Group P）. The model of pulmonary fibrosis was established through intratracheally instillation with bleomycin （3.5mg/kg） except group C. Their pathological section of lung tissues were harvested for hemotoxylin and eosin stain and Masson＇s trichrome stain, so as to observe the degree of pulmonary fibrosis and to determine hydroxyproline content. Therefore, it aims to examine the distribution and the expression of NOX4 in pulmonary tissues in the above three groups through immunohistochemical method. Results Masson staining showed that the degree of pulmonary fibrosis in Group M was severer than that in Group C at the 7^th, 14^th and 28^th day separately （ P 〈 0.05 ）. The degrees of pulmonary fibrosis in Group P was lower than that in Group M （ P 〈 0.05 ）. The content of hydroxyproline （Hyp） in the lung tissue of Group M was increased than that in Group C （ P 〈 0.05 ）. The contents of Hyp in Group P and N were decreased obviously compared with that in Group M respectively （ P 〈 0.05 ）. The immunohistochemical studies showed that NOX4 was mainly observed in airway smooth muscle cells, alveolar epithelial cells, lung fibroblast, vascular smooth muscle cells and endothelial cells in lung tissues with a high level expression in Group M on the 7^th, 14^th or 28^th day respectively （P 〈0.05）. Compared with that in Group M, the expression of NOX4 of the lung tissues in Group C was weaker （ P 〈 0.05 ）. The expressions of NOX4 of lung tissues in Group P was a little higher than that in Group C （P 〈 0.05）, but still lower than that in Group M （P 〈 O. 05）. Conclusion NOX4 was widely expressed in pulmonary fibrosis. The mechanism of up - reglation of the expression of NOX4 may participate in pulmonary fibrosis induced by bleomycin. The pirfenidone can alleviate the degree of pulmonary fibrosis induced by bleomycin, and can play active roles in down - regulating the expression of NOX4. It suggests that NOX4 may become the new target in the treatment of pulmonary fibrosis.
出处
《医学研究杂志》
2016年第5期164-169,共6页
Journal of Medical Research
