关键词: 气管干细胞, 5-氟尿嘧啶, 组蛋白去乙酰化酶1, 分子开关, 免疫组织化学, 免疫印迹法, 人

Abstract: P>Objective To determine the expression and changes of histone deacetylase 1(HDAC1) during human bronchial regeneration after injury and to explore the molecular mechanisms in proliferation and differentiation of the bronchial stem cells. Methods The isolated human bronchial epithelium was injured by 5\|fluorouracil(5-FU). HDAC1 expression in bronchial epithelium during the process of regeneration was analyzed by immunohistochemistry and Western blotting. Results 1.At 0 hour after 5-FU treatment, the bronchial epithelium shed and the expression of HDAC1 was negative. During 3-6 hours after the removal of 5-FU,the bronchial rings were covered with flattened epithelial cells and a few of the epithelial cells were HDAC1 positive. At the 12th hour, the epithelial cells were cuboidal and merged into pieces. The number of the HDAC1 positive cells increased obviously and a few HDAC1 positive cells were around one negative cell. At the 24th hour, the epithelial cells continued to increase and became stratified,HDAC1 was in top expression throughout all layers at this time; At the 48th hour, the epithelium restored similar to the pseudostratified structure,HDAC1 decreased slightly; The expression of HDAC1 was negative in normal bronchial epithelium. 2.Western blotting analysis showed that there were different HDAC1 levels at different times after the removal of 5-FU which in accordance with the change of immunohistochemistry. Conclusion With more differentiating cells appeared, more HDAC1 positive cells were observed, suggesting that HDAC1 can function as a molecular switch of bronchial epithelial stem cells fom proliferation to differentiation./P>

Key words: Bronchial stem cell, 5-Fluorouracil, Histone deacetylase 1, Molecular switch, Immunohistochemistry, Western blotting, Human