肺纤维化进程中肺泡上皮细胞进行性减少的动态变化:P16,CyclinD1,CDK4的参与及作用?(英文)  

Role of P16,CyclinD1,and CDK4 in progressive reduction of alveolar epithelial cells during pulmonary fibrosis

作　　者：郑金旭[1] 吕晓婷[2] 

机构地区：[1]江苏大学附属医院呼吸科,江苏省镇江市212001 [2]江苏大学临床医学院,江苏省镇江市212001

出　　处：《中国组织工程研究与临床康复》2010年第41期7779-7783,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：the Science Research Foundation of Ministry of Health,No.wkj2006-0-026;the "333" Project of Jiangsu Province,No.2007-16-09~~

摘　　要：背景:研究发现肺纤维化进程中肺组织肺泡上皮细胞进行性减少,但其原因不明。课题组设想在肺纤维化进程中可能存在P16,CyclinD1,CDK4蛋白异常表达,P16-CyclinD1/CDK4细胞周期调控通路异常可能参与肺纤维化肺泡上皮细胞减少过程。目的:研究P16,CyclinD1,CDK4在博来霉素诱导的小鼠肺纤维化肺组织中的动态表达及其意义。方法:向6周龄KM小鼠气管内注射博莱霉素制备肺纤维化模型,对照组给予等体积的生理盐水。分别于造模后的第3,7,14和28天,苏木精-伊红染色观察肺组织的病理形态改变;免疫组织化学及Western blot检测肺组织P16,CyclinD1,CDK4蛋白的表达。结果与结论:模型组小鼠肺组织出现典型的纤维化改变,肺组织P16,CDK4蛋白表达随时间增加而增强,CyclinD1蛋白表达随时间增加而减少。与对照组比较,模型组P16,CDK4蛋白阳性细胞数增多,P16蛋白量于造模后14,28d多于对照组(P<0.01),而CDK4蛋白量于造模后7,14,28d多于对照组(P<0.05);CyclinD1蛋白阳性细胞数及蛋白量于造模后3,7d多于对照组(P<0.05),而28d则明显少于对照组(P<0.05),造模后14d,模型组的CyclinD1蛋白阳性细胞数多于对照组,而蛋白量少于对照组(P<0.05)。说明在肺纤维化进程中存在P16,CyclinD1,CDK4蛋白异常表达,P16-CyclinD1/CDK4细胞周期调控通路异常可能是肺纤维化肺泡上皮细胞减少的重要原因。BACKGROUND： Several studies have demonstrated that the number of alveolar epithelial cells decreases gradually as pulmonary fibrosis develops, but the reasons remain unknown. The expression of P16, CyclinD1, and CDK4 might be abnormal and P16-CyclinD1/CDK4 cell cycle regulatory pathway may play an important role in the progressive reduction of alveolar epithelial cells during pulmonary fibrosis. OBJECTIVE： To investigate the dynamic expression of P16, CyclinD1, and CDK4 in the pulmonary tissue of bleomycin-induced pulmonary fibrosis mice. METHODS： Pulmonary fibrosis was induced in 6-week-old KM mice by intratracheal injection of bleomycin （BLM group）. The control mice were administered the same volume of physiological saline （control roup）. At 3, 7, 14, and 28 days after modeling, hematoxylin-eosin staining was performed to observe the pathomorphological changes of lung tissue. P16, CyclinD1, and CDK4 protein expression in lung tissue was detected by immunohistochemistry and Western blot analysis. RESULTS AND CONCLUSION： In the BLM group, typical changes of pulmonary fibrosis were observed, and P16 and CDK4 protein expression in the pulmonary tissue increased with time, but CyclinD1 protein expression was decreased with time. P16 and CDK4 protein-positive cells in the BLM group were more than in the control group. Compared with the control group, P16 protein expression in the BLM group was higher at 14 and 28 days after modeling （P0.01） and CDK4 protein expression was higher at 7, 14, and 28 days after modeling （P0.05）. CyclinD1 protein-positive cells and protein expression were greater at 3 and 7 days after modeling in the BLM group （P 0.05）, but they were less at 28 days after modeling （P0.05）, than in the control group. At 14 days after modeling, CyclinD1 protein-positive cells in the BLM group were more, but CyclinD1 protein expression was less, than in the control group （P0.05）. These findings suggest that P16, CyclinD1 and CDK4 protein expression was abnormal during pulmo

关 键 词：肺纤维化 小鼠 P16 CYCLIND1 CDK4 

分 类 号：R318[医药卫生—生物医学工程]