宫内炎性预敏及生后高氧暴露对早产大鼠肺细胞肺p53和细胞周期调节因子基因表达的影响

Effects of intrauterine inflammatory presensitization and hyperoxic exposure after birth on expressions of p53 and cell cycle regulatory factor gene in pneumonocytes of premature rats

目的:观察宫内炎性预敏和生后高氧暴露对肺细胞肿瘤抑制蛋白(p53)和肺细胞周期调节因子(p21waf/cip1)基因表达的影响,探讨其与新型支气管肺发育不良(BPD)发病机制之间的关系。方法:早产大鼠随机分为生理盐水+高氧组、LPS+高氧组、LPS组和正常对照组,于生后第1、7和14天随机取8只采用逆转录聚合酶链反应技术(RT-PCR)检测各组肺组织p53及p21waf/cip1mRNA的表达水平。结果:p53 mRNA表达LPS组在生后1天明显高于其他3组(P<0.01),LPS+高氧组在生后第14天明显高于其他3组(P<0.05)。p21waf/cip1mRNA的表达LPS组在生后第1天明显高于其它3组(P<0.05),LPS+高氧组在生后第14天明显高于其它3组(P<0.01)。结论:宫内炎性预敏及生后高氧暴露可能通过p53及p21waf/cip1途径抑制肺组织细胞增殖,使肺泡化进程受阻,进而可能导致新型BPD的发生。

Objective： To observe the effects of intrauterine inflammatory presensitization and hyperoxic exposure after birth on expressions of tumor suppressor protein （p53） and cell cycle regulatory factor （p21waf/eip[） gene in pneumonocytes of premature rats, explore their relationships with pathogenesis of new -type bronchopulmonary dysplasia （BPD） . Methods： The premature rats were randomly divided into normal saline ＋ hyperoxia group, lipopolysaccharide （LPS） ＋ hyperoxia group, LPS group and normal control group; RT - PCR was used to detect the expression levels of p53 and p21waf/cipl mRNA in pulmonary tissues of 8 rats randomly selected from each group on the first, the seventh and the fourteenth days after birth. Results： The expression level of p53 mRNA on the first day after birth in LPS group was statistically significantly higher than those in the other three groups （ P 〈 0.01 ）, the expression level of p53 mRNA on the fourteenth day after birth in LPS ＋ hyperoxia group was statistically significantly higher than those in the other three groups （ P 〈 0. 05 ） . The expression level of p21waf/cipl mRNA on the first day after birth in LPS group was statistically significantly higher than those in the other three groups （P 〈 0. 05 ） , the expression level of p21 waf/cipl mRNA on the fourteenth day after birth in LPS ＋ hyperoxia group was statistically significantly higher than those in the other three groups （P 〈 0. 01 ） . Conclusion： Intrauterine inflammatory presensitization and hyperoxic exposure after birth may inhibit proliferation of pneumonocytes by p53 and p21 waf/cipl pathways, block the process of pulmonary alveoli, which may contribute to the occurrence of new - type BPD.