摘要
目的研究p21基因在放射性心脏损伤(RIHD)中的作用,探讨p21基因敲除对小鼠RIHD表型的影响。方法p21^(-/-)小鼠作为实验组,p21^(+/-)小鼠为对照组。采用小动物照射研究平台对小鼠进行10 Gy全心照射,建立RIHD模型。收集照射后6周小鼠心脏标本,测量大体标本并行HE染色;Vevo2100超声成像系统检测小鼠室壁厚度及左室射血分数;缺氧探针法检测心脏组织缺氧;Tunel法检测心脏细胞凋亡。结果相较于p21^(+/-)小鼠,p21^(-/-)小鼠生存期显著缩短(P=0.004);舒张期、收缩期室间隔变薄(P=0.049、P=0.006),左室后壁增厚(P<0.001),左室射血分数下降(P=0.004);心脏组织肉眼观增大,HE染色示心脏组织炎症细胞聚集,心肌细胞排列紊乱;心脏组织缺氧和凋亡明显。结论p21^(-/-)小鼠受照后引起生存期缩短、心功能减弱、心脏结构异常、心脏组织缺氧和凋亡,表现出更严重RIHD。p21在心脏照射后的修复中起重要作用。
Objective To investigate the role of p21 gene in the radiation-induced heart disease(RIHD)and to evaluate the effect on p21 gene knockout on RIHD phenotype in mouse models.Methods p21^(-/-)mice were utilized in the experimental group,and p21^(+/-)mice were allocated in the control group.RIHD mouse models were established by exposure to 10 Gy whole heart irradiation by using a small animal radiation research platform.The heart samples were collected at 6 weeks after irradiation,the gross specimens were measured and subject to HE staining.The wall thickness and left ventricular ejection fraction of the mice were detected by the Vevo2100 ultrasound imaging system.The hypoxia in cardiac tissues was detected by the hypoxia probe method.The apoptosis of cardiac cells was determined by Tunel method.Results Compared with the p21^(+/-)mice,the survival of p21^(-/-)mice was significantly shortened(P=0.004),the interventricular septum was significantly thinned during the diastolic and systolic phases(P=0.049,P=0.006),the left ventricular posterior wall was remarkably thickened(P<0.001)and the left ventricular ejection fraction was significantly decreased(P=0.004).The gross heart tissue was enlarged in the p21^(-/-)mice.HE staining showed the aggregation of inflammatory cells in cardiac tissues and disordered arrangement of myocardial cells.Significant hypoxia and apoptosis could be observed in the p21^(-/-)mouse heart tissues.Conclusions p21^(-/-)mice are prone to more severe RIHD after irradiation,manifested with shortened cardiac survival,weakened cardiac function,abnormal cardiac structure,hypoxia and apoptosis of cardiac tissues.p21 plays an important role in the repair after cardiac irradiation.
作者
杜海洋
曾治民
徐芃
张鹏
易雅丽
黄龙
刘安文
Du Haiyang;Zeng Zhimin;Xu Peng;Zhang Peng;Yi Yali;Huang Long;Liu Anwen(Department of Oncology,The Second Affiliated Hospital of Nanchang University,Nanchang 330006,China;Zhejiang Key Laboratory of Radiation Oncology,Cancer Hospital of University of Chinese Academy of Sciences,Hangzhou 310022,China)
出处
《中华放射肿瘤学杂志》
CSCD
北大核心
2021年第1期86-89,共4页
Chinese Journal of Radiation Oncology
基金
国家自然科学基金(81560509)。
