KGF-2对COPD小鼠保护性作用的免疫学研究

Immunological study on the protective effect of KGF-2 on COPD mice

目的研究角质细胞生长因子2(keratinocyte growth factor-2,KGF-2)对慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)模型小鼠肺部炎症及免疫功能的影响。方法取15只6～8周龄(体重20～25 g)的雄性BALB/C小鼠,首先用烟熏加气道滴注脂多糖(lipopolysaccharide,LPS)的方法构建COPD模型。KGF-2组于第1天和第14天给予KGF-2,共2次。采用肺组织HE染色及肺泡灌洗液(bronchoalveolar lavage fluid,BALF)蛋白浓度评价小鼠气道炎症及肺泡壁屏障的破坏。ELISA检测小鼠血浆及BALF中IL-6和肿瘤坏死因子(tumor necrosis factorα,TNF-α)的水平。流式细胞术检测小鼠脾脏中CD4+T细胞及CD8+T细胞的比例及细胞程序性死亡蛋白1(programmed cell death protein 1,PD-1)的表达。结果与COPD组小鼠比较,KGF-2组小鼠肺部炎症细胞浸润减少,肺泡结构相对完整,肺泡灌洗液及血浆中IL-6和TNF-α水平有降低的趋势。与COPD组比较,KGF-2组小鼠脾脏中CD4+T细胞及CD8+T细胞的比例升高(P<0.05),PD-1比例降低(P<0.05)。结论 KGF-2可能具有抑制COPD相关肺组织炎症及增强免疫功能的作用。

Objective To study the effect of keratinocyte growth factor 2 （KGF 2） on the lung inflammation in a mouse model of chronic obstructive pulmonary disease （COPD）. Methods Fifteen BALB/C mice were randomly and equally divided into control,COPD and COPD with KGF 2 treatment groups. The COPD groups were exposed to cigarette smoke and lipopolysaccharide （LPS） instillation, and KGF2 was instilled on day 1 and day 14 for KGF2 group. The airway inflammationand alveolar barrier damage were evaluated by HE staining and bronchoalveolar lavage fluid （BALF） protein concentration respectively. The expression of IL 6 and TNF a in plasma and BALF were detected by ELISA. The percentage of CD4 ＋ T cells, CD8 ＋ T cells and the expression of programmed cell death protein 1 （PD 1） in spleen of mice were detected by flow cytometry. Results Compared with the COPD mice,infiltration of inflammatory cells in the lungs and levels of IL6 and tumor necrosis factor （TNF α） in alveolar lavage fluid and plasma were slightly decreased in KGF2 group, with complete aveolar structure. CD4 ＋ T cells and CD8 ＋ T cells in the spleen increased （P〈0. 05）, PD 1 ratio decreased （P〈0.05）compared with the COPD mice. Conclusions KGF 2 has the effect of inhibiting COPD inflammation and enhancing immune function.