Zhenwu Decoction Attenuates Water-Retention–Related Phenotypes and Multiorgan Injury in Rats With Doxorubicin-Induced Chronic Heart Failure

IF 2.8 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Weijun Li, Zhenyu Zhao, Xuefeng Lin, Guoliang Chen, Lin Li, Ge Fang, Zhixi Hu
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Abstract

Objective

This study is aimed at evaluating the effects of Zhenwu Decoction (ZWD) on cardiac dysfunction, water-retention–related phenotypes, and brain and kidney injury in rats with doxorubicin-induced chronic heart failure (CHF), and at examining whether these effects were accompanied by changes in AVP, V2R, PKA-Cα, and AQP2-related markers.

Methods

Rats that met the prespecified CHF criteria after doxorubicin administration were rerandomized to the model, ZWD-L, ZWD-M, ZWD-H, or tolvaptan groups and treated once daily for 14 consecutive days. Cardiac function, biochemical and water balance–related outcomes, histopathology, brain AVP, and renal V2R, PKA-Cα, and AQP2 expression were assessed. The animal was the experimental unit, and the number analyzed is reported for each outcome.

Results

Compared with the control group, model rats showed impaired cardiac function; increased ascites and tissue water retention; reduced 24-h urine output; histological injury in the heart, brain, and kidney; and altered AVP, V2R, PKA-Cα, and AQP2-related markers. ZWD treatment was associated with improvement in these measured outcomes, with the magnitude and statistical support varying across doses. Tolvaptan produced the expected aquaretic reference response. Adjusted p values and the number of animals analyzed are reported for each outcome.

Conclusion

In this doxorubicin-induced CHF model, ZWD improved cardiac function and water-retention–related phenotypes and was accompanied by changes in AVP, V2R, PKA-Cα, and AQP2-related markers. These data support an association but do not establish pathway mediation, direct target engagement, or heart–brain–kidney crosstalk.

珍五汤减轻阿霉素诱导的慢性心力衰竭大鼠的水潴留相关表型和多器官损伤。
目的:本研究旨在评价真武汤(ZWD)对阿霉素诱导的慢性心力衰竭(CHF)大鼠心功能障碍、水潴留相关表型及脑、肾损伤的影响,并探讨其是否伴随AVP、V2R、PKA-Cα、aqp2相关标志物的改变。方法:将阿霉素给药后符合预先设定的CHF标准的大鼠重新随机分为模型组、ZWD-L组、ZWD-M组、ZWD-H组和托伐普坦组,每天1次,连续14 d。评估心功能、生化和水平衡相关结果、组织病理学、脑AVP、肾V2R、PKA-Cα和AQP2表达。动物为实验单位,并为每个结果报告分析的数字。结果:与对照组比较,模型大鼠心功能受损;腹水和组织水潴留增加;24小时排尿量减少;心、脑、肾的组织学损伤;AVP、V2R、PKA-Cα和aqp2相关标志物改变。ZWD治疗与这些测量结果的改善有关,其幅度和统计支持因剂量而异。Tolvaptan产生了预期的水样参考响应。对每个结果报告调整后的p值和分析的动物数量。结论:在阿霉素诱导的CHF模型中,ZWD改善了心功能和水潴留相关表型,并伴有AVP、V2R、PKA-Cα和aqp2相关标志物的改变。这些数据支持一种关联,但未建立通路介导、直接靶点参与或心-脑-肾串扰。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cardiovascular Therapeutics
Cardiovascular Therapeutics 医学-心血管系统
CiteScore
5.60
自引率
0.00%
发文量
55
审稿时长
6 months
期刊介绍: Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged. Subject areas include (but are by no means limited to): Acute coronary syndrome Arrhythmias Atherosclerosis Basic cardiac electrophysiology Cardiac catheterization Cardiac remodeling Coagulation and thrombosis Diabetic cardiovascular disease Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF) Hyperlipidemia Hypertension Ischemic heart disease Vascular biology Ventricular assist devices Molecular cardio-biology Myocardial regeneration Lipoprotein metabolism Radial artery access Percutaneous coronary intervention Transcatheter aortic and mitral valve replacement.
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