单次趋化素样因子1导入所致小鼠肺病变的转归及其意义

目的 研究单次趋化素样因子1(CKLF1)导人所致小鼠肺病变的转归及其意义.方法 120只BALB/c小鼠随机分为实验组和对照组,每组60只.实验组小鼠股四头肌内注入自行构建的pcDNA3.1-CKLF1-Myc-His表达质粒(CKLF1质粒)100 μg,对照组小鼠相同部位注入pcDNA3.1-Myc-His空质粒100μg,注入后均给予局部电脉冲刺激.质粒导人后第1、4、8周末每组各处死20只小鼠,观察并比较2组支气管肺泡灌洗液(BALF)及肺组织的病理学变化.结果 导入质粒后1和4周,实验组小鼠BALF中中性粒细胞分别为(35.0±5.2)%和(22.9±2.2)%,淋巴细胞分别为(34.5±2.8)%和(22.0±2.0)%,均明显高于对照组中性粒细胞(6.7±2.2)%、(7.0±2.4)%,淋巴细胞(5.9±1.6)%、(6.1±2.7)%,均P<0.01].肺组织病理学检查显示,CKLF1质粒导人后1周小鼠气道上皮细胞脱落,肺间质充血水肿、炎细胞渗出;4周可见肺泡间隔增厚,中性粒细胞、巨噬细胞及成纤维细胞明显增生,大量胶原纤维沉积于肺间质;8周可见肺组织病变明显减轻,肺泡结构渐趋恢复.结论 CKLF1可引起支气管肺组织的炎性损伤,单次CKLF1导入所致肺病变可自行逆转.

Outcome and significance of pulmonary pathological changes induced by a single intramuscular injection of chemokine-like factor 1 in mice

Objective To investigate the significance of pathological changes in murine lung by a single intramuscular injection of chemokine-like factor 1 (CKLF1). Methods A total of 120 gender-matched BALB/c mice were randomly and evenly divided into treatment group and control group (60 in each). One hundred nanomilligram of pcDNA3. 1-CKLF1-Myc-His, CKLF1-expressing plasmid, in 100 μl of pyrogen-free saline was injected into the anterior tibial muscle of mice followed by the delivery of electric pulses. Mice in the control group received 100 μg of pcDNA3.1-Myc-His in 100 μl of pyrogen-free saline. At the end of week 1,4 and 8 respectively after injection of CKLF1, 20 mice were sacrificed in every group and the cellular profiles in bronchoalveolar lavage fluid (BALF) and the pulmonary pathological changes were observed. Results At the end of week 1 and 4 respectively after CKLF1 injection, the neutrophils (35.0±5.2) % and (22.9±2.2)% respectively] and lymphocytes (34.5±2.8) % and (22.0± 2.0)% respectively] in BALF of the treatment group were higher than those of the control group neutrophils: (6.7±2.2)% and (7.0±2.4)% respectively, lymphocytes: (5.9±1.6)% and (6.1± 2.7) % respectively, all P < 0.01]. Pathological studies demonstrated shedding of bronchiolar epithelium, congestion and edema in interstial tissue and inflammatory cell infiltration in mice at 1 week after CKLF1 injection. Week 4 after CKLF1 administration, the alveolar wall was shown significantly thickened with proliferation of neutrophils, macrophages and fibroblasts as well as remarked collagen deposition in the interstitium. At the end of week 8 after CKLF1 administration, the remarkable morphological changes of the lung gradually subsided and the structure of the lung returned to normal. Conclusions CKLF1 causes injury of inflammation and remodeling in airway in mice. The pulmonary pathological changes induced by a single intramuscular injection of CKLF are reversible.