p21 gene knockout aggravates radiation-induced heart disease in vivo
Du Haiyang1, Zeng Zhimin1, Xu Peng1, Zhang Peng2, Yi Yali1, Huang Long1, Liu Anwen1
1Department of Oncology, The Second Affiliated Hospital of Nanchang University,Nanchang 330006, China; 2Zhejiang Key Laboratory of Radiation Oncology, Cancer Hospital of University of Chinese Academy of Sciences, Hangzhou 310022, China
Abstract：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 10Gy 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.
Du Haiyang,Zeng Zhimin,Xu Peng et al. p21 gene knockout aggravates radiation-induced heart disease in vivo[J]. Chinese Journal of Radiation Oncology, 2021, 30(1): 86-89.
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