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目的近年来研究发现慢性肺疾病(CLD)早产儿支气管肺泡灌洗液中转化生长因子-β1(TGF-β1)水平明显升高,但其表达在CLD发生、发展中动态变化规律及与CLD的肺泡发育障碍的关系尚不明确。该研究探索高氧致CLD肺组织TGFβ1基因及蛋白表达特点及对其肺发育的影响。方法采用高浓度氧诱导早产鼠CLD模型,应用反转录聚合酶链反应(RTPCR)、免疫组织化学及图像分析等技术,动态观察肺系数、放射状肺泡计数(RAC)的变化,并同时测定肺组织TGF-β1mRNA及蛋白表达水平。结果生后1d,3d,两组肺系数、RAC无差异(P>0.05),7d和14d时实验组肺系数、RAC低于对照组(P<0.05),21d时RAC明显降低(P<0.001),但两组肺系数无差异;实验组肺组织TGFβ1mRNA水平3d高于对照组(P=0.005),14d达高峰(P<0.001),21d稍有下降,但仍高于对照组(P=0.005);实验组肺组织TGFβ1蛋白表达7d增高(P=0.036),21d达高峰(P<0.001);肺组织TGF-β1蛋白表达与RAC呈显著负相关(P=0.003)。结论暴露高氧环境中早产鼠肺组织TGF-β1蛋白表达的动态变化与其肺发育障碍的程度相一致,TGF-β1是抑制肺泡发育的重要因子。
OBJECTIVE: In recent years, the level of transforming growth factor-β1 (TGF-β1) in bronchoalveolar lavage fluid in preterm infants with chronic lung disease (CLD) has been significantly increased, but the dynamic changes of the expression of TGF-β1 in CLD The relationship between alveolar dysplasia is not yet clear. This study explored the characteristics of TGFβ1 gene and protein expression in hyperoxia-induced CLD lung and its effects on lung development. Methods CLD models of premature rats were induced by hyperoxia and the changes of lung coefficient and radial alveolar count (RAC) were observed dynamically by reverse transcription polymerase chain reaction (RTPCR), immunohistochemistry and image analysis. The pulmonary Tissue TGF-β1 mRNA and protein expression levels. Results After 1 and 3 days of birth, the pulmonary coefficient and RAC of the two groups were not significantly different (P> 0.05). On the 7th and 14th day, the pulmonary coefficient and RAC in the experimental group were lower than those in the control group (P <0.05) ), But there was no difference in lung coefficient between the two groups. The level of TGFβ1 mRNA in the experimental group was higher than that in the control group 3d (P = 0.005), reached the peak at 14d (P <0.001), slightly decreased at 21d but still higher than that of the control group (P = 0.005). The expression of TGFβ1 protein in lung tissue of experimental group increased at 7d (P = 0.036) and peaked at 21d (P <0.001). The expression of TGF-β1 in lung tissue was negatively correlated with RAC (P = 0.003). Conclusions The dynamic changes of TGF-β1 protein expression in the lung tissue of premature rats exposed to hyperoxia are consistent with the degree of pulmonary dysplasia. TGF-β1 is an important factor in inhibiting alveolar development.