高氧致慢性肺疾病早产鼠的肺组织CDK4、p21动态变化及其意义

Expression and Significance of CDK4 and p21 in Premature Rats with Hyperoxia-induced Chronic Lung Disease

目的探讨CDK4及p21在高氧诱导早产鼠慢性肺疾病(CLD)形成中动态表达规律及对CLD肺纤维化的影响,完善CLD发生机制及研究新的防治策略。方法将80只新生早产SD大鼠随机分为实验组(FiO2为90%)和对照组(FiO2为21%)。分别采用免疫组化SABC方法检测特定时间点1,3,7,14,21d大鼠肺组织CDK4、p21蛋白表达并进行肺组织纤维化评分。结果实验组14,21d肺纤维化评分明显高于对照组;肺组织CDK4蛋白表达明显高于对照组,其与肺纤维化评分呈明显正相关;p21蛋白表达明显低于对照组,其与肺纤维化评分呈明显负相关。结论高氧可诱导早产鼠的肺组织CDK4表达增强及抑制p21表达,其异常表达可能是导致肺成纤维细胞过度增殖,最终发生肺间质纤维化的重要原因。

Objective To explore the expression and significance of CDK4 and p21 in premature rats with hyperoxia-induced chronic lung disease （CLD） is very important for new strategies of prevention and treatment of CLD. Methods Eighty premature rats were randomly divided into 2 groups：the model group with CLD induced by hyperoxia（90% FiO2,n = 40）,and the control group （21% FiO2,n = 40）. The expressions of CDK4 and p21 were determined by using immunohistochemical methods and the degrees of interstitial fibrosis in lung were evaluated. Results On the 14th and 21st days after hyperoxia,scores of interstitial fibrosis in lung in the model group were significantly higher than those in the control group. The level of CDK4 expression in the model group was significantly higher than that in the control group, and the expression of CDK4 was positively correlated with score of interstitial fibrosis in lung. The level of p21 expression in the model group was significantly lower than that in the control group, and the expression of p21 was negatively correlated with score of interstitial fibrosis in lung. Conclusion Hyperoxia may induce the expression of CDK4 and suppress the expression of p21 in premature rats, the abnormal expression of CDK4 and p21 might result in over-proliferation of lung fibroblast,which ultimately develops into interstitial fibrosis in lung.