β连环素在吸烟小鼠气道上皮损伤修复中的作用

The role of β-catenin in the repair of the damaged airway epithelium in smoking mice

目的 研究 β连环素 (β cat)在吸烟小鼠不同阶段气道上皮中表达的变化 ,探讨不同功能状态的β cat在气道上皮损伤修复中的作用。 方法 采用HE染色光镜观察研究小鼠吸烟 5周组(S5w组 ) ,吸烟 10周组 (S10w组 ) ,吸烟 15周组 (S15w组 )气道上皮的形态学变化 ;应用原位杂交及免疫组化技术研究气道上皮 β catmRNA、β cat、原癌基因 (c Src)、酪氨酸磷酸化蛋白 (phosphorytyrsine,p Tyr)的表达。结果 (1)随着吸烟时间的延长气道上皮形态学上呈损伤 (S5w)、修复 (S10w)、过度增殖 (S15w)变化。 (2 )S5w、S10w、S15w组 β catmRNA及蛋白表达水平均较对照组低 (对照组、S5w、S10w、S15w组 β cat染色平均吸光度值分别为 0 2 0 4± 0 0 12、0 0 97± 0 0 0 7、0 16 0± 0 0 0 3、0 10 7±0 0 0 8;β catmRNA染色平均吸光度值分别为 0 2 2 3± 0 0 0 8、0 12 3± 0 0 11、0 173± 0 0 0 8、0 116± 0 0 0 4,P <0 0 1)。但S10w组 β catmRNA及蛋白表达水平较S5w、S15w组高。S15w组中尚可见 β cat核内表达。 (3)正常气道上皮细胞c Src、p Tyr表达极弱 ,和S5w、S10w、S15w组相比差异有显著性 (对照组、S5w、S10w、S15w组c Src染色平均吸光度值分别为 0 0 48± 0 0 15、0 12 7± 0 0 18?

Objective To evaluate the role of β-catenin(β-cat) in the repair of the damaged airway epithelium by comparing their expressions of β-cat in different stages of smo king in murine model.Methods With HE staining,morphological changes of airway epithelium were observed micr oscopically in mice model at 5th week(S5 w),10th week (S10 w) and 15th week (S15 w) of smoking. Immunohistochemistry and hybridization in situ were perform ed to investigate the expressions of β-cat mRNA, β-cat, c-Src gene and phos pho-rytyrosine-protein (p-Tyr). Results Morp hological changes of the airway epithelium showed predominant damage(S5 w), rep ai r(S10 w) and excessive proliferation (S15 w) Mean β-cat OD values at S5 w, S10 w and S15 w were 0.097±0.007, 0160±0003 and 0.107±0.008, being signif ica ntly lower than the control value(0204±0012, all P<001); The mean β -cat mRNA OD value of S5 w, S10 w and S15 w were (0123±0011,0173±0008 and 01 16±0004) were also lower than that in control(0223±0008, all P<001 ), but the OD value of S10 w w as higher than those of S5 w and S15 w. OD value of S15 w was the lowest with only traced β-cat mRNA expression in the nuclei. The expressions of c-Src an d p-Tyr in normal airway epithelium(OD values:0048±0015, 0075±0011) were significantly lower than those in S5 w(0127±0018,0112±0012), S10 w(0147±0010, 0.127±0 018) and S15 w(0147±0010, 0127±0018, all P<0001). Conclusion β-cat may play an important role in the proc ess of repair of airway epithelium. Downregulation of β-cat may be caused by c -Src which phosphorylates tyrosin residues of β-cat, leading to its degradati on ; Intracellular level of p-Tyr may, to some extent, reflect the functional cond ition of β-cat.