Heart failure (HF) is often complicated by renal dysfunction. Tolvaptan and valsartan are two well-known agents for the treatment of HF. However, the role of tolvaptan/valsartan combination on HF with renal dysfunction remains unclear. To establish a mice model with HF with renal dysfunction, mice were intraperitoneally injected with doxorubicin (Dox). Echocardiogram was applied to assess the left ventricular function. Additionally, serum aldosterone (ALD) and angiotensin II (Ang II) level in mice were determined by ELISA. Meanwhile, western blot assay was used to evaluate the expressions of B cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax) and cleaved caspase 3 in the heart and kidney tissues of mice. In this study, we found that compared to tolvaptan or valsartan alone treatment group, tolvaptan/valsartan combination obviously improved the left ventricular ejection fraction (LVEF) and the left ventricular fractional shortening (LVFS), and reduced serum ALD and Ang II level in Dox-treated mice. Additionally, tolvaptan/valsartan combination significantly prevented the inflammation and fibrosis of heart and kidney tissues in Dox-treated mice. Meanwhile, tolvaptan/valsartan combination notably inhibited the myocardial and renal cell apoptosis in Dox-treated mice via upregulation of Bcl-2 and downregulation of Bax and cleaved caspase 3, compared to the single drug treatment. Collectively, tolvaptan/valsartan combination could improve cardiac and renal functions, as well as prevent the fibrosis, inflammation and apoptosis of heart and kidney tissues in Dox-treated mice. Taken together, combining tolvaptan with valsartan might be a promising approach to achieve enhanced therapeutic effect for treatment of HF with renal dysfunction.

中文翻译：

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托伐普坦和缬沙坦的组合可改善多柔比星诱导的小鼠心力衰竭的心脏和肾脏功能。

心力衰竭 (HF) 往往并发肾功能不全。托伐普坦和缬沙坦是治疗 HF 的两种众所周知的药物。然而，托伐普坦/缬沙坦组合对 HF 伴肾功能不全的作用仍不清楚。为了建立伴有肾功能不全的 HF 小鼠模型，给小鼠腹腔注射多柔比星 (Dox)。应用超声心动图评估左心室功能。此外，小鼠血清醛固酮 (ALD) 和血管紧张素 II (Ang II) 水平通过 ELISA 测定。同时，采用western blot法检测B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）和cleaved caspase 3在小鼠心脏和肾脏组织中的表达。在这项研究中，我们发现与单用托伐普坦或缬沙坦治疗组相比，托伐普坦/缬沙坦组合显着改善了 Dox 治疗小鼠的左心室射血分数 (LVEF) 和左心室缩短分数 (LVFS)，并降低了血清 ALD 和 Ang II 水平。此外，托伐普坦/缬沙坦组合可显着预防 Dox 治疗小鼠心脏和肾脏组织的炎症和纤维化。同时，与单一药物治疗相比，托伐普坦/缬沙坦组合通过上调 Bcl-2 和下调 Bax 和裂解半胱天冬酶 3 显着抑制 Dox 治疗小鼠的心肌和肾细胞凋亡。总的来说，托伐普坦/缬沙坦组合可以改善心脏和肾脏功能，并防止 Dox 治疗小鼠心脏和肾脏组织的纤维化、炎症和细胞凋亡。综合起来，