CAJ | 학술논문

目的观察前列腺素E2(PGE2)通过调控高迁移率族蛋白-1(HMGB1)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、1 000 mol/L)或不同时间作用下(0、3、6、12、24 h)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HMGB1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1 000 mol/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HMGB1由胞核向胞质外的迁移,且PGE2调控HMGB1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.
목적 관찰전렬선소E2(PGE2)통과조공고천이솔족단백-1(HMGB1)재심기세포적핵전위종이영향심기비후적발생발전,병탐토기궤제.방법 체외배양유서심기세포,검측내피소-1(ET-1)재불동농도(0、1、10、100、1 000 mol/L)혹불동시간작용하(0、3、6、12、24 h)대심기세포분비PGE2적영향;가입PGE2억제제신타미신,검측기대ET-1유도심기비대적영향;대심기세포진행분조(n=6),단독혹동시가입ET-1、PGE2화신타미신등,검측기대심기세포내HMGB1표체화전위적영향.결과 리체심기세포중,ET-1가이촉진PGE2적분비,구유제량의뢰성,ET-1농도위1 000 mol/L시PGE2분비량최고,체도(165.3±26.9) ng/L;동시구유시간의뢰성,ET-1작용시간위12h시PGE2분비량최고,위(174.4±15.4) ng/L;내원성혹외원성적PGE2균구유촉진ET-1유도심기비대발전적작용,가입PGE2억제제신타미신현저강저ET-1유도적심기세포표면적증대(P＜0.05).ET-1화PGE2균촉진HMGB1유포핵향포질외적천이,차PGE2조공HMGB1적핵전화주요유기수체EP4개도.결론 PGE2통과기수체EP4재ET-1유도적심기비대과정중발휘작용.
Objective To investigate the role of prostaglandin E2 (PGE2) in regulating High mobility group box1 (HMGB1) expression and location in cardiomyocytes,as well as the effects on the development 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 cardiomyocytes was detected.PGE2 inhibitor indomethacin was used to test the effect of PGE2 on ET-1 induced 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-dependent 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 hypertrophy.We also found that EP4 receptor,rather than EP1-3 receptor,mediated the functions of PGE2 during the process.Conclusion PGE2 could promote the development of ET-1-induced cardiac hypertrophy via modulating the location of HMGB1 in cardiomyocytes via EP4.