探讨Lyn激酶对慢性阻塞性肺疾病(COPD)小鼠的作用及其可能机制。

将C57BL/6j野生型小鼠与C57BL/6j Lyn⁺转基因小鼠分别随机分为野生型对照组(WT组)、野生型模型组(WT+COPD组)、Lyn⁺对照组(Lyn⁺组)、Lyn⁺模型组(Lyn⁺+COPD组)，每组各8只小鼠。WT+COPD组与Lyn⁺+COPD组小鼠采用香烟熏吸加气道内注入脂多糖法进行COPD造模，60 d后采用肺功能检测仪记录小鼠相关肺功能指标，HE染色观察小鼠肺组织病理形态变化，ELISA法检测血清与肺泡灌洗液(BALF)中IL-1β、IL-6、IL-10与TNF-α的含量，Western blot检测肺组织中Erk-sp1信号通路相关蛋白表达水平。

WT组与Lyn⁺组小鼠肺组织无明显病变现象，WT+COPD组肺组织中肺泡结构破坏，出现大量炎性细胞浸润，Lyn⁺+COPD组小鼠肺组织的病变情况较WT+COPD组小鼠明显减轻。与WT组小鼠比较，WT+COPD组小鼠的Ri升高，Cdyn与FEV0.3%/FVC下降，血清和BALF中IL-1β、IL-6、IL-10、TNF-α的含量增加，肺组织中pErk、Erk、sp1蛋白水平增加，差异均具有统计学意义(P<0.05)；与Lyn⁺组比较，Lyn⁺+COPD组Ri升高而Cdyn、FEV0.3%/FVC下降，血清和BALF中IL-1β、IL-6、IL-10、TNF-α的含量增加，肺组织中pErk、Erk、sp1蛋白水平增加，差异均具有统计学意义(P<0.05)；与WT+COPD组比较，Lyn⁺+COPD组Ri下降而Cdyn与FEV0.3%/FVC有所上升，IL-1β、IL-6、IL-10、TNF-α的含量降低，肺组织中pErk、Erk、sp1的蛋白水平降低，差异均具有统计学意义(P<0.05)。

Lyn激酶通过抑制炎症反应来减轻小鼠COPD，其机制可能与Erk-sp1信号通路密切相关。

To study the effect of Lyn kinase on the mice with chronic obstructive pulmonary disease (COPD) and its possible mechanism.

C57BL/6j wild type mice and C57BL/6j Lyn⁺ transgenic mice were randomly divided into a wild type control group (WT group, n=8), a wild type model group (WT+ COPD group, n=8), a Lyn⁺ control group (Lyn+ group, n=8), and a Lyn+ model group (Lyn⁺ + COPD group, n=8). The mice in the WT+ COPD group and the Lyn⁺ + COPD group were modeled by COPD using cigarette smoking and lipopolysaccharide injection into the airway. And 60 days later, the related lung function indicators were recorded by a lung function tester, the pathological changes in the lung tissues were observed with HE staining, the contents of IL-1β, IL-6, IL-10 and TNF-α in the serum and in the alveolar lavage fluid (BALF) were detected with ELISA method, and the expression of Erk-sp1 signaling pathway-related proteins in the lung tissues was detected with Western blotting method.

The lung tissues of the mice in the WT group and in the Lyn+ group had no obvious pathological changes. The alveolar structure in the lung tissues of the WT+ COPD group was damaged, and a large number of inflammatory cell infiltration occurred. The pulmonary alveolar rupture and inflammatory cell infiltration in the Lyn⁺ + COPD group were improved compared with that of the WT+ COPD group. In the WT+ COPD group, Ri increased, Cdyn and FEV 0.3%/FVC decreased, the contents of IL-1β, IL-6, IL-10 and TNF-α in the serum and BALF were all increased, pErk, Erk and sp1 protein levels in the lung tissues increased compared with the WT group, and the differences were statistically significant between the two groups (P<0.05). In the Lyn⁺ + COPD group, Ri was increased while Cdyn and FEV0.3%/FVC were decreased, and the levels of IL-1β, IL-6, IL-10 and TNF-α in the serum and BALF were increased, the protein levels of pErk, Erk and sp1 increased in the tissues compared with the Lyn+ group, and the differences were statistically significant between the two groups (P<0.05). In the Lyn⁺ + COPD group, Ri decreased while Cdyn and FEV0.3%/FVC increased, the contents of IL-1β, IL-6, IL-10 and TNF-α decreased, the protein levels of pErk, Erk and sp1 decreased compared with the WT+ COPD group, and the differences were statistically significant between the two groups (P<0.05).

Lyn kinase can alleviate COPD in mice by inhibiting the inflammatory response, and its mechanism may be closely related to Erk-sp1 signaling pathway.