不同浓度β1-肾上腺素受体自身抗体对心肌细胞存活影响的差异性

Differences in cardiomyocytes’ survival by anti-β1-adrenergic receptor autoantibodies of different concentrations

目的观察不同浓度的β1-肾上腺素受体自身抗体(β1-adrenergic receptor autoantibodies,β1-AA)作用不同时间,对于心肌细胞产生的不同终末效应。方法分别使用10^-10、10^-9、10^-8、10^-7、10^-6 mol/Lβ1-AA作用于乳鼠心肌细胞(neonatal rat cardiomyocytes,NRCMs)和H9c2细胞检测细胞生存率(24、36、48 h),作用于H9c2细胞检测线粒体功能(ATP含量、线粒体膜电势)(48 h)。结果中、高浓度(10^-7、10^-6 mol/L)β1-AA刺激各个时间,NRCMs、H9c2细胞生存率明显降低;而低浓度(10^-10、10^-9、10^-8 mol/L)使得H9c2细胞轻微增生。高浓度(10^-6 mol/L)β1-AA刺激后,H9c2细胞中ATP含量降低,而中低浓度(10^-10、10^-9、10^-8、10^-7 mol/L)β1-AA使H9c2细胞中ATP含量增加。高浓度β1-AA(10^-6 mol/L)刺激后,H9c2细胞线粒体膜电势降低,低浓度(10^-10、10^-8 mol/L)β1-AA则使H9c2细胞线粒体膜电势增加。结论高浓度β1-AA刺激心肌细胞后表现为损伤作用,低浓度刺激表现为正性作用(即增强线粒体功能、促存活),与作用时间无明显相关,本研究为β1-AA阳性人群中心功能差异的现象提供了病理生理学依据。

Objective To investigate the terminal effects on cardiomyocytes ofβ1-adrenergic receptor autoantibodies(β1-AA)at different concentrations for different time.Methods Cell survival was detected after 10^-10,10^-9,10^-8,10^-7,10^-6 mol/Lβ1-AA treating neonatal rat cardiomyocytes(NRCMs)and H9c2 cells for 24,36,and 48 hours,while mitochondrial function(ATP content and mitochondrial membrane potential)of H9c2 cells was detected after 48 hours.Results The cell survival of NRCMs and H9c2 decreased significantly byβ1-AA in high-concentrations(10^-7,10^-6 mol/L)at any time and the survival of H9c2 proliferated slightly in low concentrations(10^-10,10^-9,10^-8 mol/L)at any time.ATP content of H9c2 was decreased byβ1-AA in high concentration(10^-6 mol/L),while increased in medium and low concentrations(10^-10,10^-9,10^-8,10^-7 mol/L).The mitochondrial membrane potential of H9c2 was decreased byβ1-AA in high concentrations(10^-6 mol/L),while increased in low concentrations.Conclusionβ1-AA damage cardiomyocytes in high concentration while it showed the positive effects in low concentrations(ie,promoting ATP production and cell survival).And all the effects had no relation to time.In conclusion,our study provides a new foundation for the differences of cardiac function amongβ1-AA positive population.