探讨LncRNA CDKN2B-AS1/CDKN2A和p53在小鼠特发性肺纤维化及肺癌组织中的表达及意义。

选取48只SPF级雄性野生C57BL/6小鼠，随机平均分为正常组、肺纤维化组、肺癌组及肺纤维化合并肺癌组，建立肺纤维化模型、肺癌模型以及肺纤维化合并肺癌模型，分别留取各组小鼠肺组织及血液标本。通过HE染色、Masson染色观察肺组织纤维化程度，PCR法检测CDKN2B-AS1、CDKN2A mRNA在各组中的表达，Western-Blot法检测CDKN2A、p53蛋白在各组中的表达，分析CDKN2B-AS1与CDKN2A和p53表达的相关性。多组间的比较采用单因素方差分析，进一步两两比较采用LSD-t检验；两变量间的关系采用Pearson相关性分析。

所有动物模型均建立成功，各组小鼠肺组织HE染色、Masson染色均符合实际情况。4组小鼠肺组织CDKN2A及p53蛋白表达水平的差异均有统计学意义（F=80.295、75.190，P<0.01）；其中肺纤维化组、肺癌组及肺纤维化合并肺癌组CDKN2A及p53蛋白表达水平均明显低于对照组（P<0.01），肺纤维化合并肺癌组CDKN2A及p53蛋白表达水平也明显低于肺纤维化组和肺癌组（P<0.01）。4组小鼠肺组织CDKN2B-AS1及CDKN2A mRNA表达水平的差异均有统计学意义（F=605.981、3 404.438，P<0.01）；其中肺纤维化组、肺癌组及肺纤维化合并肺癌组CDKN2B-AS1和CDKN2A mRNA的表达水平明显低于正常组（P<0.01），肺纤维化合并肺癌组CDKN2A mRNA的表达水平明显低于肺纤维化组和肺癌组（P<0.01），肺纤维化合并肺癌组CDKN2B-AS1表达水平明显低于肺纤维化组（P<0.01）。4组小鼠肺组织CDKN2B-AS1的表达水平与CDKN2A和p53的表达水平均呈正相关（r=0.981、0.874、0.856、0.992，0.986、0.984、0.994、0.992；P<0.01）。

LncRNA CDKN2B-AS1可能是通过调控其邻近基因CDKN2A影响p53信号通路，从而导致肺纤维化合并肺癌的风险增高。

To explore the Expression and significance of LncRNA CDKN2B-AS1/CDKN2A and p53 in idiopathic pulmonary fibrosis and lung cancer in mice.

48 SPF male C57BL/6 mice were randomly divided into normal group, pulmonary fibrosis group, lung cancer group and pulmonary fibrosis combined with lung cancer group, and all the models were established. Lung tissue and blood samples were collected from each group. The degree of pulmonary fibrosis was observed by HE staining and Masson staining. The expressions of CDKN2B-AS1 and CDKN2A mRNA in each group were detected by PCR. The expressions of CDKN2A and p53 proteins in each group were detected by Western blot. The correlation between CDKN2B-AS1 and the expressions of CDKN2A and p53 was analyzed. Univariate analysis of variance was used for comparison among multiple groups, and LSD-t test was used for further pairwise comparison. The relationship between the two variables was analyzed by Pearson correlation.

There were significant differences in the expression levels of CDKN2A and p53 protein in the lung tissues among the four groups (F=80.295, 75.190, P < 0.01). The expression levels of CDKN2A and p53 protein in pulmonary fibrosis group, lung cancer group and pulmonary fibrosis combined with lung cancer group were significantly lower than those in the control group (P < 0.01). The expression levels of CDKN2A and p53 protein in pulmonary fibrosis combined with lung cancer group were also significantly lower than those in pulmonary fibrosis group and lung cancer group (P < 0.01). There were significant differences in the expression levels of CDKN2B-AS1 and CDKN2A mRNA in the lung tissues among the four groups (F=605.981, 3404.438, P < 0.01). The expression levels of CDKN2B-AS1 and CDKN2A mRNA in pulmonary fibrosis group, lung cancer group and pulmonary fibrosis combined with lung cancer group were significantly lower than those in normal group (P < 0.01), the expression level of CDKN2A mRNA in pulmonary fibrosis combined with lung cancer group was significantly lower than that in pulmonary fibrosis group and lung cancer group (P < 0.01), and the expression level of CDKN2B-AS1 in pulmonary fibrosis combined with lung cancer group was lower than that in pulmonary fibrosis group (P < 0.01). The expression levels of CDKN2B-AS1 in lung tissue of four groups were positively correlated with the expression levels of CDKN2A and p53 (r = 0.981, 0.874, 0.856, 0.992; r = 0.986, 0.984, 0.994, 0.992; P < 0.01).

LncRNA CDKN2B-AS1 may affect p53 signal pathway by regulating its adjacent gene CDKN2A, resulting in increased risk of pulmonary fibrosis and lung cancer.