前列腺素E2对内皮素-1诱导心肌肥厚的影响  

The role of prostaglandin E2 in the development of edothelin - 1 - induced cardiac hypertrophy

作　　者：刘刚琼[1] 李凌[1] 张金盈[1] 赵晓燕[1] 王蕴哲[1] 陈安琪[1] 薛瑞[2] 

机构地区：[1]郑州大学第一附属医院心内科,450052 [2]郑州大学第一附属医院泌尿外科,450052

出　　处：《中华实验外科杂志》2015年第8期1837-1839,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（U1304804）

摘　　要：目的观察前列腺素E2（PGE2）通过调控高迁移率族蛋白．1（HMGBl）在心肌细胞的核转位从而影响心肌肥厚的发生发展，并探讨其机制。方法体外培养乳鼠心肌细胞，检测内皮素．1（ET-1）在不同浓度（0、1、10、100、1000mol／L）或不同时间作用下（0、3、6、12、24h）对心肌细胞分泌PGE2的影响；加入PGE2抑制剂吲哚美辛，检测其对ET-1诱导心肌肥大的影响；对心肌细胞进行分组（n=6），单独或同时加入ET-1、PGE2和吲哚美辛等，检测其对心肌细胞内HMGBl表达和转位的影响。结果离体心肌细胞中，ET-1可以促进PGE2的分泌，具有剂量依赖性，ET．1浓度为1000mol／L时PGE2分泌量最高，达到（165．3±26．9）ng／L；同时具有时间依赖性，ET-1作用时间为12h时PGE2分泌量最高，为（174．4±15．4）ng／L；内源性或外源性的PGE2均具有促进ET-1诱导心肌肥大发展的作用，加入PGE2抑制剂吲哚美辛显著降低ET-1诱导的心肌细胞表面积增大（P〈0．05）。ET-1和PGE2均促进HMGBl由胞核向胞质外的迁移，且PGE2调控HMGBl的核转化主要由其受体EP4介导。结论PGE2通过其受体EP4在ET-1诱导的心肌肥大过程中发挥作用。Objective To investigate the role of prostaglandin E2 （PGE2） in regulating High mobility group boxl （ HMGB1 ） expression and location in cardiomyocytes, as well as the effects on the de- velopment of edothelin - 1 （ ET - 1 ） - induced cardiac hypertrophy. Methods Primary cultured neonatal rat cardiomyocytes were used as the experimental subjects. The impact of ET - 1 at different concentrations （0, 1, 10, 100,1 000 mol/L） and different time points （0, 3, 6, 12, 24 h） on PGE2 secretion in car- diomyocytes was detected. PGE2 inhibitor indomethacin was used to test the effect of PGE2 on ET - 1 in- duced cardiac hypertrophy. Results The production of PGE2 from cultured rat neonatal cardiomyocytes was significantly increased in response to ET - 1 stimulation. A dose - dependent manner [ PGE2 secretion was highest when ET - 1 concentration was 1 000 nmol/L, reaching （ 165.3 ±26. 9） ng/L] and time - de- pendent manner （PGE2 secretion was highest when the incubation time of ET - 1 was 12 h, reaching 174. 4 ± 15.4） were observed. In contrast, inhibition of PGE2 synthesis with endomethacin abolished ET- 1 -induced hypertrophic responses （P 〈 0. 05）. Furthermore, HMGB1 translocation from nucleus to cytoplasm was also demonstrated to be involved in the development of ET - 1 - induced cardiac hypertro- phy. We also found that EP4 receptor, rather than EP1 -3 receptor, mediated the functions of PGE2 dur- ing the process. Conclusion PGE2 could promote the development of ET - 1 - induced cardiac hypertro- phy via modulating the location of HMGB1 in cardiomyocytes via EP4.

关 键 词：前列腺素E2 内皮素-1 高迁移率族蛋白-1 心肌肥大 

分 类 号：R719.31[医药卫生—妇产科学]