p300在老年小鼠心房颤动易感性中的作用研究  

Role of p300 in susceptibility of atrial fibrillation in aged mice

作　　者：彭德威 周慧珊 刘海燕 高小燕 赖颖瑜 李巧巧 邓春玉 杨慧[2] 邝素娟[2] 薛玉梅[2] 吴书林[1,2] 饶芳 PENG De-wei;ZHOU Hui-shan;LIU Hai-yan;GAO Xiao-yan;LAI Ying-yu;LI Qiao-qiao;DENG Chun-yu;YANG Hui;KUANG Su-juan;XUE Yu-mei;WU Shu-lin;RAO Fang(School of Medicine, South China University of Technology, Guangzhou 510006, China;Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital Medical Research Center, Guangdong Academy of Medical Sciences, Guangzhou 510080, China;School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China)

机构地区：[1]华南理工大学医学院,广东广州510006 [2]广东省心血管病研究所心内科,广东省人民医院医学研究部,广东省医学科学院,广东广州510080 [3]南方医科大学药学院,广东广州510515

出　　处：《中国药理学通报》2021年第2期180-186,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81670314,81870254);广州市科技计划项目(No 201804010059)。

摘　　要：目的探讨转录辅激活因子p300在调控老年小鼠心房肌细胞电重塑,进而导致房颤中的作用。方法分别收集5、13和18月龄的C57BL/6小鼠左心耳组织,Western blot检测p300蛋白,钙通道蛋白和衰老信号通路相关蛋白的表达。分别取5月龄和18月龄小鼠,分离单个心房肌细胞,全细胞膜片钳技术检测各组细胞的L型钙电流(L-type calcium current,ICa,L)和动作电位时程(action potential duration,APD)。快速起搏心房观察不同月龄小鼠房颤的可诱发性。结果与5月龄小鼠相比,13和18月龄小鼠左心房组织p300、衰老相关信号通路蛋白p53和p21表达明显增加(P<0.05),而L型钙通道蛋白Cav1.2表达减少;老年小鼠心房肌细胞ICa,L电流密度明显减小,APD缩短。不同剂量的p300抑制剂-姜黄素(50、100 mg·kg^-1·d-1)饲养后能明显减少老年小鼠房颤的可诱发率,并使衰老小鼠心房肌细胞的ICa,L密度增加和APD延长(P<0.05)。结论p300可能通过调控ICa,L参与衰老相关心房肌细胞电重塑。Aim To explore the role of co-transcriptional activator p300 in regulating the electrical remodeling of atrial myocytes in aging mouse,which resulted in atrial fibrillation.Methods The left atrial appendage tissues of 5,13 and 18-month-old C57BL/6 mice were collected respectively.Western blot was used to detect the protein expression levels of p300,L type calcium channel(Cav1.2)and aging related protein p53/p21.Acute enzymatic hydrolysis was used to isolate single atrial myocytes,and the whole-cell patch-clamp technique was used to detect the L-type calcium current(ICa,L)and action potential duration(APD)of atrial myocytes.The susceptibility of atrial fibrillation was detected by electrophysiological examination.Results Compared with 5-month-old mice,the protein expression of p300,p53 and p21 in the left atrial appendage of mice increased in 13-month-old and 18-month-old C57BL/6 mice(P<0.05),while the expression of Cav1.2 decreased.The peak current of ICa,L in atrial myocytes of 18-month-old C57BL/6 mice was significantly reduced,and the APD was shortened.Treatment of p300 inhibitor-curcumin(50,100 mg·kg^-1·d-1)significantly reduced the inducible rate of atrial fibrillation through increasing ICa,L and prolonging APD of atrial myocytes in elderly mice(P<0.05).Conclusion p300 may participate in the aging-induced electrical remodeling of atrial myocytes by regulating ICa,L.

关 键 词：p300蛋白 心房肌细胞 细胞衰老 L型钙电流 动作电位时程 姜黄素 

分 类 号：R-332[医药卫生—人体解剖和组织胚胎学] R322.11[医药卫生—基础医学]