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激素替代疗法与衰老：一种针对与年龄相关的氧化应激和心脏重构的潜在治疗方法。

Hormone Replacement Therapy and Aging: A Potential Therapeutic Approach for Age-Related Oxidative Stress and Cardiac Remodeling.

机构信息

Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged H-6726, Hungary.

Interdisciplinary Excellence Centre, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary.

出版信息

Oxid Med Cell Longev. 2021 Feb 3;2021:8364297. doi: 10.1155/2021/8364297. eCollection 2021.

DOI:10.1155/2021/8364297
PMID:33623635
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7875635/
Abstract

Advanced age is an independent risk factor for cardiovascular diseases, which might be further exacerbated by estrogen deficiency. Hormone replacement therapy (HRT) decreases cardiovascular risks and events in postmenopausal women; however, its effects are not fully elucidated in older individuals. Thus, the aim of our study is to examine the impact of HRT on oxidant/antioxidant homeostasis and cardiac remodeling. In our experiment, control (fertile) and aging (~20-month-old) female Wistar rats were used. Aging rats were further divided into estrogen- (E, 0.1 mg/kg/day ) or raloxifene- (RAL, 1.0 mg/kg/day ) treated subgroups. After 2 weeks of treatment, cardiac heme oxygenase (HO) activity, total glutathione (GSH) content, matrix metalloproteinase-2 (MMP-2) activity, and the concentrations of collagen type I and tissue inhibitor of metalloproteinase (TIMP-2), as well as the infarct size, were determined. The aging process significantly decreased the antioxidant HO activity and GSH content, altered the MMP-2/TIMP-2 signaling, and resulted in an excessive collagen accumulation, which culminated in cardiovascular injury. However, 2 weeks of either E or RAL treatment enhanced the antioxidant defense mechanisms and attenuated cardiac remodeling related to aging. Our findings clearly show that 2-week-long HRT is a potential intervention to bias successful cardiovascular aging via reducing oxidative damage and cardiovascular dysfunction.

摘要

高龄是心血管疾病的独立危险因素，而雌激素缺乏可能进一步加剧这种风险。激素替代疗法（HRT）可降低绝经后妇女的心血管风险和事件；然而，其在老年人中的作用尚未完全阐明。因此，我们的研究旨在探讨 HRT 对氧化应激/抗氧化平衡和心脏重构的影响。在我们的实验中，使用了对照（有生育能力）和衰老（~20 月龄）的雌性 Wistar 大鼠。衰老大鼠进一步分为雌激素（E，0.1mg/kg/天）或雷洛昔芬（RAL，1.0mg/kg/天）治疗亚组。治疗 2 周后，测定心脏血红素加氧酶（HO）活性、总谷胱甘肽（GSH）含量、基质金属蛋白酶-2（MMP-2）活性以及胶原 I 型和基质金属蛋白酶抑制剂（TIMP-2）的浓度，以及梗死面积。衰老过程显著降低了抗氧化 HO 活性和 GSH 含量，改变了 MMP-2/TIMP-2 信号，导致胶原过度积累，最终导致心血管损伤。然而，2 周的 E 或 RAL 治疗增强了抗氧化防御机制，减轻了与衰老相关的心脏重构。我们的研究结果清楚地表明，2 周的 HRT 是一种通过减少氧化损伤和心血管功能障碍来促进成功心血管衰老的潜在干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6876/7875635/665a217fbbc1/OMCL2021-8364297.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6876/7875635/2b314dfe9d02/OMCL2021-8364297.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6876/7875635/f3279d6e3db9/OMCL2021-8364297.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6876/7875635/e84ba716761e/OMCL2021-8364297.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6876/7875635/a28efdd24679/OMCL2021-8364297.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6876/7875635/665a217fbbc1/OMCL2021-8364297.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6876/7875635/2b314dfe9d02/OMCL2021-8364297.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6876/7875635/f3279d6e3db9/OMCL2021-8364297.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6876/7875635/e84ba716761e/OMCL2021-8364297.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6876/7875635/a28efdd24679/OMCL2021-8364297.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6876/7875635/665a217fbbc1/OMCL2021-8364297.006.jpg

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