过表达p53对机械负荷导致的心肌细胞肥大反应的影响  

The Effect of p53 Overexpression on Cardiomyocytes Hypertrophy Induced by Mechanical Stress

作　　者：胡海锋[1] 邹云增[2] 张书宁[1] 张磊[1] 葛均波[1] 

机构地区：[1]复旦大学附属中山医院,上海市心血管病研究所,上海200032 [2]复旦大学生物医学研究院,上海200032

出　　处：《中国临床医学》2008年第4期445-448,共4页Chinese Journal of Clinical Medicine

基　　金：国家杰出青年科学基金(30525018);高等学校博士点专项基金(20060246079)

摘　　要：目的:观察心肌细胞内过表达p53对机械牵张引起的心肌细胞肥大反应的影响。方法:使用大鼠乳鼠来源的心肌细胞,对贴壁培养在硅胶培养皿内的心肌细胞进行0min、5min、10min、30min、1h和2h的机械牵张,以Western blot法检测心肌细胞肥大反应相关蛋白激酶细胞外信号调节激酶1/2(ERK1/2)在不同时间牵张后磷酸化水平变化的时间特点;将含p53基因的重组腺病毒载体(p53-Adv)转染心肌细胞使之高表达p53蛋白,再行同样的不同时间的机械牵张,观察磷酸化ERK1/2表达的时间变化特点;最后将两部分结果对比以明确p53过表达对机械牵张后ERK1/2磷酸化变化的影响。结果:未行p53-Adv转染时5min牵张组磷酸化ERK1/2表达比0min牵张组明显升高(P<0.05),并且随着牵张时间的延长ERK1/2磷酸化水平逐步增高;而p53-Adv转染后,5min牵张组磷酸化ERK1/2表达较0min牵张组仍增加(P<0.05),但更长时间牵张组较0min牵张组ERK1/2磷酸化水平不升反降(P<0.05),以2h组最低(P<0.05)。结论:心肌细胞内过表达p53后,虽然不影响短期牵张(5min)的ERK1/2磷酸化水平的升高,但明显抑制更长时间牵张后的磷酸化ERK1/2表达,提示心肌细胞内的p53对机械负荷后晚期的心肌肥厚反应有抑制作用,p53可能与心肌肥厚由代偿期向失代偿期的转化有关。Objective： To observe the effects of p53 overexpression on the hypertrophic response induced by mechanical stretch. Methods：The neonatal rat-derived cardiomyocytes were cultured in six sillicon plates and individually stretched for 0 min、5min、10min、30min,1 h and 2 h. P- ERK1/2 expression in cardiomyocytes was measured by Western Blot to observe its expression changes after being stretched for different time;Cardiomyocytes were induced to overexpress p53 after being trans-fected by Adenovirus including p53 gene（p53-Adv）. Then the transfected cells were individually stretched for the same time as mentioned above. P-ERK1/2 was measured to observe the P-ERK1/2 expression alternation after different time stretch; At last the effects of p53 overexpression on P-ERK1/2 expression changes accompanying varying time stretch was observed by comparing the results of two parts. Results： When not being transfected, P- ERK1/2 expression in 5rain group raised up significantly compared with the non-stretch group （P〈0.05）, and it increased more and more with stretch time elongation. After p53-Adv transfection, P- ERK1/2 expression still raised after 5 rain stretch （P〈0.05）. But p-ERK1/2 expression level inversely dropped （P〈0.05）, with the 2h group being the lowest （P〈0.05）. Conclusion：The elevation of p-ERK1/2 expression after short time stretch（5min） can not be inhibited by p53 overexpression, but p53 significantly suppressed P-ERK1/2 expression after longger time stretch. It implied that p53 played an inhibitory role in myocardiohypertrophy induced by mechanical stress in advanced stage and may be involved in the transition from compansated hypertrophy to decompansated state.

关 键 词：心肌细胞 肥大反应 机械牵张 P53 ERK1/2 

分 类 号：R542.2[医药卫生—心血管疾病]