CyclinD1和p21^(CIP1)在大鼠肺发育过程中的动态表达

Dynamic expression of Cyclin D1 and p21^(CIP1) during lung development in rats

目的细胞周期素D1(CyclinD1)、p21CIP1是主要的肺细胞增殖调控蛋白,参与肺发育、肺损伤修复过程。本研究观察大鼠肺发育过程中小管期、囊泡期、肺泡期等不同阶段CyclinD1和p21CIP1的表达特征。方法分别于孕20 d、21 d、生后0 d、3 d、7 d、14 d、21 d取胎鼠或新生鼠肺组织标本(n=6),用免疫组织化学技术检测CyclinD1和p21CIP1在大鼠肺发育各期定位表达,免疫印迹半定量检测大鼠肺发育过程中CyclinD1和p21CIP1蛋白的表达。结果在大鼠肺发育各期中,小管期CyclinD1蛋白表达最强,肺泡期CyclinD1蛋白表达最弱。而p21CIP1蛋白表达在小管期最弱,肺泡期最强。在小管期CyclinD1阳性表达主要定位于上皮细胞,p21CIP1表达阴性。囊泡期CyclinD1表达强度明显减弱,CyclinD1和p21CIP1阳性表达主要定位于上皮细胞和间质细胞。肺泡期p21CIP1表达最强,CyclinD1阳性表达主要定位于间质细胞,p21CIP1阳性表达主要定位于上皮细胞。结论大鼠肺发育过程中CyclinD1和p21CIP1在各期表达部位及数量有差异,在小管期,CyclinD1表达最强,细胞增殖活动明显较囊泡期和肺泡期旺盛,肺泡期p21CIP1表达最强与肺泡分隔及成熟有关。

Objective CyclinD1 and p21^CIP1 are major proteins to regulate lung cell proliferation and involved in lung development and lung injury reparation.This study aimed to explore the expression manners of CyclinD1 and p21^CIP1 at canalicular,saccular and alveolar stages during lung development in Sprague-Dawley rats.Methods Lung tissues were obtained from fetal rats of 20 and 21 days gestational ages,and neonatal rats at 0,3,7,14 and 21 days（n=6）.Lung tissues were used for histopathology and the protein analysis of CyclinD1 and p21^CIP1（immunohistochemistry and Western blot）.Results The strongest expression of CyclinD1 and the weakest expression of p21^CIP1 occurred at 20-21 days gestation（canalicular stage）.At the canalicular stage,CyclinD1 was mainly expressed in epithelial cells,and the expression of p21^CIP1was negative.At the saccular stage,the expression of CyclinD1 decreased significantly and the p21^CIP1 expression increased significantly.Positive expression of CyclinD1 and p21^CIP1 was found in epithelial cells and interstitial cells.At the alveolar stage,the CyclinD1 expression was the lowest and the p21^CIP1 expression was the highest.The positive expression of CyclinD1 was found in interstitial cells and that of p21^CIP1 was found in epithelial cells.ConclusionsThe location and quantity of CyclinD1 and p21^CIP1 expression are different at various stages during lung development in rats.A strongest CyclinD1 expression found in the canalicular stage may be associated a high lung cell proliferation.A strongest p21^CIP1 expression found in the alveolar stage may be associated with alveolar maturity.