BPD新生大鼠cyclinA2及其抑制因子的表达和对肺泡发育的影响

Expression of cyclin A2 and its inhibitory factor in BPD neonatal rats and its effect on alveolar development

目的探讨高氧致新生大鼠支气管肺发育不良(bronchopulmonary dysplasia,BPD)发生过程中肺组织细胞周期蛋白cyclinA2及其抑制因子p21对肺泡发育的影响。方法80只新生大鼠随机分为模型组(FiO2=80%-85%)和对照组(FiO2=21%)。采用辐射状肺泡计数(axial acinar count,RAC)和肺泡间隔厚度评价肺泡发育程度;免疫组织化学和Western blot检测cyclinA2和p21分布及表达。结果RAC从3d开始低于对照组,肺泡间隔厚度从7d开始高于对照组(P<0.05 );模型组p21蛋白表达于3d开始增加,14d达峰,并且持续至21d,而模型组cyclinA2蛋白表达于14d、21d高于对照组(P<0.05);模型组中RAC与p21蛋白表达呈负相关(r=-0.5966,P<0.01),与cyclinA2无相关性(r=0.7276,P>0.05);对照组RAC与p21无相关性(r=-0.2929,P>0.05),与cyclinA2呈正相关(r=0.8476,P<0.01);模型组和对照组肺泡间隔厚度均与p21呈正相关(r=0.4291,P<0.05;r=0.4447,P<0.05),与cyclinA2呈负相关(r=-0.6814,P<0.01;r=-0.7636,P<0.01)。结论暴露高氧新生鼠肺组织细胞周期调控蛋白cyclinA2及其抑制因子p21表达失衡,可能是干扰BPD肺泡发育的相关因素之一。

Objective To investigate the effects of cyclinA2 and its inhibitor p21 on alveolar development in bronchopulmonary dysplasia(BPD) neonatal rats. Methods Eighty newborn rats were randomly divided into a model group(FiO2=80%-85%) and a control group(FiO2=21%). The degree of alveolar development was evaluated by radial alveolar count(RAC) and alveolar septal thickness.The distribution and expression of cyclinA2 and p21 were detected by immunohistochemistry and Western blot. Results The RAC value of the model group was lower than that of the control group from 3 days.The thickness of the alveolar septum was higher than that of the control group from 7 days(P<0.05). The expression of p21 protein in the model group began to increase from 3d, peaked on 14d, and lasted for 21d.The expression of cyclinA2 protein in model group was higher than that in control group at 14d and 21d(P<0.05). There was a negative correlation between RAC and p21 protein expression in model group(r=-0.5966, P<0.01), and no correlation with cyclinA2(r= 0.7276, P>0.05);there was no correlation between RAC and p21 in the control group(r=-0.2929, P>0.05), and positively correlated with cyclinA2(r=0.8476, P<0.01). The alveolar septal thickness of the model group and the control group were both positively correlated with p21(r=0.4291, P<0.05;r=0.4447, P<0.05), and negatively correlated with cyclinA2(r=-0.6814, P<0.01;r=-0.7636, P<0.01). Conclusion The imbalance of cell cycle regulatory protein cyclinA2 and its inhibitor p21 expression in neonatal rats exposed to hyperoxia may be one of the related factors that interfere with the development of BPD alveoli.