FIZZ1在吸烟大鼠COPD模型肺组织的表达及与气道炎症的相关性研究

目的:探讨FIZZ1在吸烟大鼠慢性阻塞性肺疾病(COPD)模型肺组织内的表达及其与COPD慢性气道炎症的相关性。方法:选用70只雄性Wistar大鼠,采用单纯吸入香烟烟雾的方法制造大鼠COPD模型,HE染色观察大鼠肺组织病理变化鉴定造模成功。采用免疫组化定性分析及Western blot定量检测COPD大鼠肺组织中FIZZ1在不同时点的蛋白表达。对支气管肺泡灌洗液(BALF)行炎症细胞计数。酶联免疫吸附法(ELISA)检测不同时点BALF及血清中白细胞介素4(IL-4)和肿瘤坏死因子α(TNF-α)的含量。结果:HE染色显示模型组大鼠在第20周之后炎症反应呈慢性过程,并逐渐呈现COPD的病理特征。免疫组化结果显示在模型组中,FIZZ1蛋白表达随着炎症反应的加剧而显著增强,且在COPD病变组织处表达相对较强;Western blot进一步证实了免疫组化的检测结果(P0.05)。与对照组比较,模型组大鼠BALF中炎症细胞总数、中性粒细胞绝对数和淋巴细胞绝对数在第4周开始均显著升高(P0.05)。一定范围内,与对照组比较,模型组大鼠BALF及血清中炎症因子IL-4和TNF-α升高(P0.05)。结论:FIZZ1作为一种肺组织特异性炎症介质,可能参与了COPD炎症反应的发生与发展,其机制可能与诱导炎症细胞浸润和炎症因子分泌有关。

Expression of FIZZ1 on lung tissue of cigarette smoking-induced COPD rats and its relationship with airway inflammation

AIM: To investigate the expression of FIZZ1 (found in inflammatory zone 1) in the lung tissues from smoking-induced chronic obstructive pulmonary disease (COPD) rats and to explore the potential role of FIZZ1 in airway remodeling in COPD. METHODS:The male Wistar rats (n=70) were used in the study. The rats were randomly divided into COPD group and control group. The rat model of COPD was established by inhaling cigarette smoke alone. HE staining was used to observe the pathological changes of the lung tissues for firming the successful modeling. The protein expression of FIZZ1 in the lung tissues at different time points was determined by immunohistochemistry and Western blot. The inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted. The concentrations of interleukin 4 (IL-4) and tumor necrosis factor α (TNF-α) in both BALF and serum were measured by ELISA. RESULTS: HE staining showed that the inflammatory response was chronic in the lung tissues of model group at 20th week and gradually showed pathological features of COPD. The results of immunohistochemistry and Western blot showed that in the model group, FIZZ1 protein expression was significantly increased (P<0.05). Total number of inflammatory cells in BALF in the cigarette smoked rats was significantly higher from 4th week (P<0.05). Within a certain range, compared with the control group, the concentrations of inflammatory cytokines IL-4 and TNF-α in both BALF and serum were increased in the model group (P<0.05). CONCLUSIONS: FIZZ1 may be involved in the occurrence and development of COPD with the mechanism of causing infiltration of inflammatory cells and secretion of cytokines.