The Effects Of P27^Kip1 Knockout In Myocardial Aging And Apoptosis Caused By Estrogen Deficiency

Objective:To assess the effects of p27 ^kip1 knockout in myocardial aging caused by estrogen deficiency through building a mice model for menopause.Material and method:Bilateral ovariectomy?OVX?was performed as a model for menopause in wild type?WT?and p27 knockout(p27^-/-)mice,respectively.Six months after operation,echocardiography was performed to assess cardiac function.Histological stain and immunohistochemistry was performed to detect the cellular senescence and apoptosis.Western blot and RT-PCR were performed to assess the relative mechanism.Results:Compared with WT control group,myocardial fibrosis and heart weight/body weight ratio of mice in WT OVX group and p27^-/-group were significantly increased,Echocardiography showed that the left ventricular diameter and volume of WT OVX group increased significantly compared with WT control mice,and the cardiac function decreased.However,there was no significant difference in the results of echocardiography between the two p27^-/-groups.Compared with the control group,the percentage of?-gal and 8-OHdG positive cells in OVX group increased significantly,the expression of p16 and p19 were significantly up-regulated,and the anti-aging indicator Bmi-1 was significantly decreased.However,in the p27^-/-group,the percentage of?-gal and 8-OHdG positive cells were significantly decreased,while the expression of p16 and p19 was decreased,while the expression of Bmi-1 was increased.Compared with the WT control group,the expression of apoptosis index Bax in WT OVX group increased significantly,the expression of anti-apoptosis index Bcl-2 was decreased significantly,and the expression of antioxidant indexes SOD1 and SOD2 were decreased significantly.However,the expression of Bcl-2,SOD1 and SOD2 were up-regulated and Bax was down-regulated in p27^-/-mice.Conclusion:Estrogen deficiency increased oxidative stress and apoptosis,accelerated aging of heart.p27 ^kip1ip1 gene deficiency can partly delay the aging and apoptosis of heart through up-regulated antioxidant enzymes.