Department of General Practice, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei.
Eur J Histochem. 2022 Nov 11;66(4):3563. doi: 10.4081/ejh.2022.3563.
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.
心力衰竭（HF）常伴有肾功能障碍。托伐普坦和缬沙坦是两种治疗 HF 的常用药物。然而，托伐普坦/缬沙坦联合治疗伴有肾功能障碍的 HF 的作用尚不清楚。为建立伴有肾功能障碍的 HF 小鼠模型，将小鼠腹腔内注射多柔比星（Dox）。应用超声心动图评估左心室功能。此外，通过 ELISA 测定小鼠血清醛固酮（ALD）和血管紧张素 II（Ang II）水平。同时，通过 Western blot 检测小鼠心脏和肾脏组织中 B 细胞淋巴瘤-2（Bcl-2）、Bcl-2 相关 X（Bax）和裂解型半胱天冬酶 3 的表达。本研究发现，与托伐普坦或缬沙坦单药治疗组相比，托伐普坦/缬沙坦联合治疗明显改善了 Dox 处理小鼠的左心室射血分数（LVEF）和左心室缩短分数（LVFS），降低了血清 ALD 和 Ang II 水平。此外，托伐普坦/缬沙坦联合治疗明显预防了 Dox 处理小鼠心脏和肾脏组织的炎症和纤维化。同时，与单药治疗相比，托伐普坦/缬沙坦联合治疗通过上调 Bcl-2 下调 Bax 和裂解型半胱天冬酶 3，显著抑制了 Dox 处理小鼠的心肌和肾脏细胞凋亡。总之，托伐普坦/缬沙坦联合治疗可改善心肾功能，预防 Dox 处理小鼠心脏和肾脏组织的纤维化、炎症和细胞凋亡。综上所述，将托伐普坦与缬沙坦联合使用可能是一种有前途的方法，可增强治疗伴有肾功能障碍的 HF 的疗效。
