博来霉素诱导的小鼠肺纤维化组织中组蛋白3和组蛋白4乙酰化变化

Changes of acetylation of histone 3 and histone 4 in bleomycin-induced pulmonary fibrosis in mice

目的探索肺纤维化发病过程中组蛋白3、组蛋白4乙酰化的变化。方法博来霉素气管给药诱导C57BL/6J雄性小鼠发生肺纤维化(博来霉素组),另外设立盐水组和正常对照组,每组16只小鼠。取肺组织进行病理学评分评价肺泡炎和肺纤维化。给药后第7,14,21天用Western blot法检测组织细胞组蛋白3、组蛋白4乙酰化水平。结果给药后第7天和第14天博来霉素组组蛋白3乙酰化率显著低于盐水组(0.855±0.183 vs 1.037±0.142,P=0.041;0.797±0.224 vs 1.186±0.160,P=0.000),而在第21天两组无显著差异(0.927±0.159 vs 0.951±0.103,P=0.832)。给药后第7天和第14天博来霉素组组蛋白4乙酰化率显著低于盐水组(0.976±0.091 vs 1.094±0.121,P=0.006;0.932±0.026 vs 1.017±0.060,P=0.045),而在第21天两组无显著差异(1.002±0.044 vs 0.980±0.068,P=0.662)。组蛋白3乙酰化率与肺泡炎评分呈负相关(r=-0.458,P=0.002)。组蛋白4乙酰化率与肺泡炎(r=-0.495,P=0.001)、肺纤维化(r=-0.396,P=0.010)病理评分均呈负相关。结论组蛋白4乙酰化水平在肺纤维化时下降,可能广泛参与肺泡炎、肺纤维化过程。

Objective To investigate the changes of acetylation of histone 3 and histone 4 in bleomycin-induced pulmonary fibrosis.Methods Sixteen C57BL/6J male mice were given bleomycin via trachea to induce the pulmonary fibrosis in bleomycin group.Mice were administrated with saline in saline group,and given no treatment in control group,and 16 mice were enrolled in each group.Histopathological score was applied to assess the severity of pulmonary fibrosis and alveolitis.Western blot was conducted to detect the acetylation levels of histone 3 and histone 4 in the lung tissues at day 7,14,21 after administration.Results The acetylation rate of histone 3 in bleomycin group was significantly lower than that in saline group at day 7(0.855±0.183 vs 1.037±0.142,P=0.041)and day 14(0.797±0.224 vs 1.186±0.160,P=0.000),but there was no significant difference at day 21(0.927±0.159 vs 0.951±0.103,P=0.832).The acetylation rate of histone 4 in bleomycin group was significantly lower than those in saline group at day 7(0.976±0.091 vs 1.094±0.121,P=0.006)and day 14(0.932±0.026 vs 1.017±0.060,P=0.045),but there was no significant difference at day 21(1.002±0.044 vs 0.980±0.068,P=0.662).The acetylation rate of histone 3 was negatively correlated with alveolitis pathological score(r=-0.458,P=0.002).The acetylation rate of histone 4 was negatively correlated with alveolitis pathological score(r=-0.495,P=0.001)and fibrosis pathological score(r=-0.396,P=0.010).Conclusion Acetylation of histone 4 is decreased during pulmonary fibrosis,and may widely participate in the progress of alveolitis and pulmonary fibrosis.