CAJ | 학술논문

目的研究心力衰竭(心衰)大鼠心肌β3,肾上腺素能受体(β3-AR)变化,观察选择性β3-AR抑制剂(SR59230A)对β3-AR、氧化应激状态的影响.方法将异丙肾上腺素(ISO)诱导的心衰大鼠随机分成ISO组(18只)与ISO+SR59230A组(21只),同时以正常大鼠为对照组(7只).ISO+SR59230A组给予SR59230A,每日2次腹腔注射;ISO组给予相应生理盐水1 ml;对照组不予处置.6周后测定心功能、心肌β3-AR、内皮型一氧化氮合酶(eNOS)、小三磷酸鸟苷结合蛋白(Racl)mRNA、蛋白表达及脂质过氧化物(LPO)、总超氧化物歧化酶(T-SOD)指标.结果心衰大鼠心功能恶化,心肌β3-AR mRNA表达增加,SR59230A可改善心功能,降低β3-AR mRNA表达(均为P<0.05).心衰时,eNOS、Racl mRNA及蛋白上调,LPO产生增加、T-SOD水平降低.SR59230A降低eNOS、Racl表达,增加心肌组织T-SOD水平,使LPO减少(均为P<0.05).结论心衰时,β3-AR表达增加,加重心肌氧化应激反应,恶化心功能.β3-AR抑制剂改善心功能可能通过抑制氧化应激、延缓心衰进展来实现.
목적 연구심력쇠갈(심쇠)대서심기β3,신상선소능수체(β3-AR)변화,관찰선택성β3-AR억제제(SR59230A)대β3-AR、양화응격상태적영향.방법 장이병신상선소(ISO)유도적심쇠대서수궤분성ISO조(18지)여ISO+SR59230A조(21지),동시이정상대서위대조조(7지).ISO+SR59230A조급여SR59230A,매일2차복강주사;ISO조급여상응생리염수1 ml;대조조불여처치.6주후측정심공능、심기β3-AR、내피형일양화담합매(eNOS)、소삼린산조감결합단백(Racl)mRNA、단백표체급지질과양화물(LPO)、총초양화물기화매(T-SOD)지표.결과 심쇠대서심공능악화,심기β3-AR mRNA표체증가,SR59230A가개선심공능,강저β3-AR mRNA표체(균위P<0.05).심쇠시,eNOS、Racl mRNA급단백상조,LPO산생증가、T-SOD수평강저.SR59230A강저eNOS、Racl표체,증가심기조직T-SOD수평,사LPO감소(균위P<0.05).결론 심쇠시,β3-AR표체증가,가중심기양화응격반응,악화심공능.β3-AR억제제개선심공능가능통과억제양화응격、연완심쇠진전래실현.
Objective To investigate the association between β3-adrenergic receptor (β3-AR) and oxidative stress in isoproterenol (ISO)-induced chronic heart failure (HF) rats. Methods Seven weight-matched normal adult rats (control), 18 ISO induced heart failure rats and 21 ISO induced heart failure rats treated with specific (β3-AR inhibitor, SR59230A for 6 weeks were included in this study. Echocardiography was performed at the end of the study and the myocardial levels of total superoxide dismutase (T-SOD) and lipid peroxidation (LPO) were measured by colorimetry, myocardial expression of (β3-AR was detected by reverse transcription-polymerase chain reaction ( RT-PCR). Result Compared with control group, the cardiac function was significantly reduced and myocardial β3-AR mRNA expression was significantly increased, LPO level was also significantly enhanced while T-SOD level was significantly reduced in ISO group and these changes could be significantly attenuated by treatment with SR59230A Conclusion Our results showed that myocardial upregulation of β3-AR is associated with increased oxidative stress in this model and β3-AR inhibitor may be a new therapeutic agent for heart failure treatment