Duan Jinhong, Esberg Lucy B, Ye Gang, Borgerding Anthony J, Ren Bonnie H, Aberle Nicholas S, Epstein Paul N, Ren Jun
Division of Pharmaceutical Sciences, University of Wyoming College of Health Sciences, Laramie, WY 82071-3375, USA.
Comp Biochem Physiol A Mol Integr Physiol. 2003 Mar;134(3):607-14. doi: 10.1016/s1095-6433(02)00347-1.
Acute ethanol exposure depresses ventricular contractility and contributes to alcoholic cardiomyopathy in both men and women chronically consuming ethanol. However, a gender-related difference in the severity of myopathy exists with female being more sensitive to ethanol-induced tissue damage. Acetaldehyde (ACA), the major oxidized product of ethanol, has been implicated to play a role in the pathogenesis and gender-related difference of alcoholic cardiomyopathy, possibly due to its direct cardiac effect and interaction with estrogen. This study was designed to compare the effects of cardiac overexpression of alcohol dehydrogenase (ADH), which converts ethanol into ACA, on the cardiac contractile response to ethanol in ventricular myocytes isolated from age-matched adult male and female transgenic (ADH) and wild-type (FVB) mice. Mechanical properties were measured with an IonOptix SoftEdge system. ACA production was assessed by gas chromatography. The ADH myocytes from both genders exhibited similar mechanical properties but a higher efficacy to produce ACA compared to FVB myocytes. Exposure to ethanol (80-640 mg/dl) for 60 min elicited concentration-dependent decrease of cell shortening in both FVB and ADH groups. The ethanol-induced depression on cell shortening was significantly augmented in female but not male ADH group. ADH transgene did not exacerbate the ethanol-induced inhibition of maximal velocity of shortening/relengthening in either gender. In addition, neither ethanol nor ADH transgene affect the duration of shortening and relengthening in male or female mice. These data suggest that females may be more sensitive to ACA-induced cardiac contractile depression than male, which may attribute to the gender-related difference of alcoholic cardiomyopathy.
急性乙醇暴露会降低心室收缩力，并导致长期饮酒的男性和女性患酒精性心肌病。然而，在肌病严重程度上存在性别相关差异，女性对乙醇诱导的组织损伤更敏感。乙醛（ACA）是乙醇的主要氧化产物，可能因其直接的心脏作用以及与雌激素的相互作用，在酒精性心肌病的发病机制和性别相关差异中发挥作用。本研究旨在比较酒精脱氢酶（ADH，可将乙醇转化为ACA）在心脏中过表达对从年龄匹配的成年雄性和雌性转基因（ADH）及野生型（FVB）小鼠分离的心室肌细胞对乙醇的心脏收缩反应的影响。使用IonOptix SoftEdge系统测量力学性能。通过气相色谱法评估ACA的产生。与FVB肌细胞相比，两种性别的ADH肌细胞表现出相似的力学性能，但产生ACA的效率更高。FVB组和ADH组暴露于乙醇（80 - 640 mg/dl）60分钟均引起细胞缩短的浓度依赖性降低。乙醇诱导的细胞缩短抑制在雌性ADH组中显著增强，而在雄性ADH组中未增强。ADH转基因在任何一种性别中均未加剧乙醇诱导的缩短/再延长最大速度的抑制。此外，乙醇和ADH转基因均未影响雄性或雌性小鼠的缩短和再延长持续时间。这些数据表明，女性可能比男性对ACA诱导的心脏收缩抑制更敏感，这可能是酒精性心肌病性别相关差异的原因。
