高氧暴露通过抑制hdacs活性影响肺发育的研究-儿科学专业论文.docxVIP

上海交通大学医学院硕士学位论文 上海交通大学医学院硕士学位论文 PAGE PAGE VIII histone acetylation and DNA methylation, and enzymes related, at present. There are not many researches concerning the epigenetic changes of BPD. It is reported that ventilation mode affects histone deacetylase 1 (HDAC1) mRNA expression, histone acetylation, and HDAC activity in the preterm lamb lung. Nasal CPAP preserves acetylation of histones whereas mechanical ventilation does not. There are epigenetic changes in the umbilical cord of neonates who happens BPD later. These results reflect that epigenetic seems to play an important role in the development of BPD. The acetylation status of histones is determined by the balance between histone acetylase (HAT) and histone deacetylase (HDACs), and directly influence the expression level of genes. We will investigate the expression and activity of HDACs in hyperoxia exposed newborn rats, and the effect of HDACs on the histological changes of hyperoxic lung injury and regulating the expression of genes. Methods: Part 1: Exposure of newborn rats to 85% concentration of oxygen to create the hyperoxic lung injury model. Study the histology and expression level of IL-8, IL-6, TNF-α, MIP-2 in hyperoxia exposed newborn rats. Part 2: Detect the expression and activity of HDACs and acetylation level of histones in hyperoxia newborn rats. Part 3: Test the indexes previously mentioned after injecting theophylline (an activator of HDACs) and / or TSA (an antagonist of HDACs) subcutaneously to exam whether hyperoxia affecting histology of lung tissues of newborn rats and whether HDACs is involved in regulating hyperoxic lung injury and the expression of IL-8, IL-6, TNF-α, MIP-2 in hyperoxia exposed newborn rats, or not. Results: There are decreased alveolar count and secondary septa count, and elevated mRNA expression of IL-8, IL-6, TNF-α, MIP-2 in hyperoxia exposed newborn rats. And the elevated expression of IL-8 was further confirmed in protein level. The expression of