越鞠丸类方治疗心衰并抑郁模型的作用及对Elk1-Ghrelin通路的影响*

作者：景云佳1，朱 妍1，高 昕2，蒋健聪1

单位：1.宜兴市中医医院，江苏 宜兴 214200； 2.江苏省中西医结合医院，江苏 南京 210028

引用：引用：景云佳，朱妍，高昕，蒋健聪.越鞠丸类方治疗心衰并抑郁模型的作用及对Elk1-Ghrelin通路的影响[J].中医药导报,2025,31(7):46-50.

DOI：10.13862/j.cn43-1446/r.2025.07.007

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摘要：

目的：探讨越鞠丸类方治疗心衰并发抑郁的作用及其对转录激活因子ETS样蛋白1（Elk1）-促生长激素释放多肽（Ghrelin）通路的影响。方法：采用冠状动脉左前降支结扎（LAD）联合慢性温和应激（CMS）法建立心衰并发抑郁小鼠模型。将60只C57BL/6小鼠随机分为6组：对照组、模型组、假手术CMS组、越鞠丸类方治疗组、AAV-mElk1组和AAV-mElk1+越鞠丸类方治疗组。通过行为学测试、超声心动图、血清学检测和分子生物学实验评估越鞠丸类方的治疗效果及其对Elk1-Ghrelin通路的影响。结果：越鞠丸类方显著改善模型小鼠的抑郁样行为，提高血清Ghrelin水平，降低B型尿钠肽（BNP）水平，改善心脏功能指标[左心室射血分数（LVEF）、左心室短轴缩短率（LVFS）、左心室舒张末期内径（LVIDd）、左心室收缩末期内径（LVIDs）、舒张早期（E峰）与晚期（A峰）血流速度比值（E/A）]。同时，越鞠丸类方下调了海马和心脏组织中Elk1 mRNA和E1K1蛋白表达水平。越鞠丸类方治疗组治疗效果最佳。海马组织中Elk1表达水平（r=-0.78，P<0.01）、心脏组织中Elk1表达水平（r=-0.82，P<0.01）均与Ghrelin呈明显负相关。结论：越鞠丸类方可能通过下调Elk1表达，提高血清Ghrelin水平，从而改善心衰并发抑郁模型小鼠的心脏功能和抑郁样行为。

关键词：心力衰竭；抑郁；越鞠丸类方；转录激活因子；ETS样蛋白1；促生长激素释放多肽；小鼠

Abstract：

Objective: To investigate the therapeutic effects of Yueju Wan derivative formula on heart failure complicated with depression and it's effect on Elk1-Ghrelin pathway. Methods: A mouse model of heart failure complicated with depression was established using left anterior descending coronary artery ligation (LAD) combined with chronic mild stress (CMS). Totally 60 C57BL/6 mice were randomly divided into six groups, including control group, model group, sham operation CMS group, Yueju Wan derivative formula treatment group, AAV-mElk1 group, and AAV-mElk1+Yueju Wan derivative formula treatment group. The therapeutic effects of Yueju Wan derivative formula and its impact on the Elk1-Ghrelin pathway were evaluated through behavioral tests, echocardiography, serological detection, and molecular biology experiments. Results: Yueju Wan derivative formula significantly improved depressive-like behaviors in model mice, increased serum Ghrelin levels, decreased BNP levels, and improved cardiac function indicators (LVEF, LVFS, LVIDd, LVIDs and E/A). Simultaneously, Yueju Wan derivative formula decreased the Elk1 mRNA and Elk1 protein expression levels in hippocampal and cardiac tissues. The Yueju Wan derivative formula treatment group showed the best therapeutic effect. The expression levels of Elk1 in hippocampal tissue (r=-0.78, P<0.01) and  Elk1 in cardiac tissue (r=-0.82, P<0.01) were negatively correlated with ghrelin. Conclusion: Yueju Wan derivative formula may improve cardiac function and depressive-like behaviors in mice with heart failure complicated with depression by down-regulating Elk1expression, thereby increasing serum Ghrelin level.

Key words：heart failure; depression; Yueju Wan derivative formula; transcriptional activator; Elk1; Ghrelin; mouse

发布时间：2026-01-06

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