非那雄胺对雄性肥胖大鼠心功能的改善作用及机制研究

Improvement Effect of Finasteride on Cardiac Function in Male Obese Rats and Its Mechanism

摘要

目的 探究非那雄胺对雄性肥胖大鼠心功能的改善作用，并分析其作用机制。方法 2023年5月至2025年5月选取雄性SD大鼠为实验对象，将给予普通饲料喂养的大鼠设为正常对照组（normal control，NC），采用高脂饲料喂养构建肥胖模型的大鼠设为肥胖实验组（high-fat，HF）；HF组造模成功后再随机分为肥胖对照组（high-fat control，HC）与非那雄胺组。非那雄胺组予以5 mg·kg^-1·d^-1非那雄胺灌胃，NC组、HC组予等体积生理盐水灌胃，连续干预14 d。观测大鼠基本形态学指标，评估大鼠心功能，采用半定量逆转录聚合酶链式反应（reverse transcription polymerase chain reaction，RT-PCR）法检测5α-还原酶2（5α-reductase 2，5α-R2）mRNA相对表达量，酶联免疫吸附试验（enzyme-linked immunosorbent assay，ELISA）法检测二氢睾酮（dihydrotestosterone，DHT）水平；蛋白质免疫印迹（western blot，WB）法检测心肌氧化应激指标水平，ELISA法检测线粒体功能指标水平。结果 干预后，非那雄胺组和HC组体重、Lee's肥胖指数、内脏脂肪组织质量均高于NC组（P < 0.05）；非那雄胺组体重高于HC组（P < 0.05）。干预后，非那雄胺组左心室射血分数（left ventricular ejection fraction，LVEF）、左心室短轴缩短率（left ventricular fractional shortening，LVFS）、左心室收缩末期内径（left ventricular end systolic diameter，LVESD）、心脏质量、谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPX4）蛋白水平、线粒体谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）水平均高于HC组，左心室后壁收缩期厚度（left ventricular posterior wall systolic thickness，LVPWs）、低频/高频心率变异性比值（low-frequency/high-frequency，LF/HF）、前列腺组织5α-R2 mRNA表达量、血清DHT水平、4-羟基壬烯醛（4-hydroxynonenal，4-HNE）蛋白水平、线粒体丙二醛（malondialdehyde，MDA）水平均低于HC组（P < 0.05）。结论 非那雄胺可改善雄性肥胖大鼠心功能，其作用可能与抑制5α-R2表达、降低DHT水平、减轻心肌氧化应激及保护线粒体功能有关。

Abstract

Objective To investigate the improvement effect of finasteride on cardiac function in male obese rats, and analyze its mechanism. Methods Male SD rats were selected as the study subjects from May 2023 to May 2025. Those fed with normal diet were assigned to the normal control group (NC group), and those fed with high-fat diet to establish obesity models were assigned to the high-fat experimental group (HF group). After successful modeling, rats in the HF group were randomly divided into the high-fat control group (HC group) and the finasteride group. Rats in the finasteride group received finasteride by gavage at 5 mg·kg^-1·d^-1, while rats in the NC group and HC group were given equal volume normal saline by gavage. The intervention lasted for 14 consecutive days. Basic morphological indicators of rats were observed, and cardiac function was evaluated, and the relative mRNA expression of 5α-reductase 2 (5α-R2) was detected by semi quantitative reverse transcription polymerase chain reaction (RT-PCR); the level of dihydrotestosterone (DHT) was measured by enzyme-linked immunosorbent assay (ELISA); the levels of myocardial oxidative stress indicators were detected by Western blot (WB), and the levels of mitochondrial function indicators were measured by ELISA.Results After intervention, body weight, Lee's obesity index and visceral adipose tissue mass in finasteride group and HC group were higher than those in NC group (P < 0.05); body weight in finasteride group was higher than that in HC group (P < 0.05). After intervention, left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-systolic diameter (LVESD), heart mass, protein level of glutathione peroxidase 4 (GPX4) and mitochondrial glutathione peroxidase (GSH-Px) level in finasteride group were higher than those in HC group. While left ventricular posterior wall systolic thickness (LVPWs), low-frequency/high-frequency ratio (LF/HF), mRNA expression of 5α-R2 in prostate tissue, serum dihydrotestosterone (DHT) level, protein level of 4-hydroxynonenal (4-HNE) and mitochondrial malondialdehyde (MDA) level were lower than those in HC group (P < 0.05). Conclusion Finasteride can improve cardiac function in male obese rats, and its mechanism may be related to inhibiting 5α-R2 expression, reducing DHT levels, alleviating myocardial oxidative stress and protecting mitochondrial function.

关键词

非那雄胺 / 肥胖症 / 心功能 / 5α-还原酶 / 氧化应激

Key words

finasteride / obesity / cardiac function / 5α-reductase / oxidative stress

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基金资助

国家自然科学基金资助项目(82200298)

2026年度市级科学技术研究与发展计划自筹经费项目(202601A183)