Liu Jian, Ji Xi-Xin, Fu Yang, Zhang Wen-Chao, Ji Hui-Fang, Liu Jian-Wei, Cheng Xiao-Shu, Dong Yi-Fei
Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
The First People's Hospital of Yongkang, Yongkang, China.
Front Cardiovasc Med. 2021 Apr 21;8:655009. doi: 10.3389/fcvm.2021.655009. eCollection 2021.
Exercising was reported by several studies to bring great benefits to heart failure with preserved ejection fraction (HFpEF), which reduced the hospitalization and the mortality of heart failure. However, the underlying mechanism of exercising on HFpEF remains unclear. In the present study, we designed and constructed a device that can perform early passive leg movement (ePLM) in rats and further observed whether treatment of ePLM exerts protective effects on HFpEF of rats. Rats were fed with high salt feed to establish an animal model of pre-clinical diastolic dysfunction (PDD), which would eventually develop into HFpEF, and then treated rats with ePLM. We conducted several experiments to evaluate the conditions of heart and blood vessel. The results show that diastolic functions of heart and blood vessel in rats were significantly improved by treatment of ePLM. We also found that pathological injuries of heart and blood vessel were ameliorated after treatment of ePLM. Moreover, treatment of ePLM decreased the protein levels of Collagen type I, Collagen type III, MMP2, and MMP9 in heart and blood vessel, indicating that cardiac and vascular fibrosis were reduced apparently by treatment of ePLM. Further investigation suggested that treatment of ePLM probably inhibit the activation of TGF-β1/Smad3 signaling pathway as well as promote the activation of Akt/eNOS signaling pathway in high salt diet induced HFpEF. In conclusion, treatment of ePLM alleviated high salt diet induced HFpEF by inhibiting fibrosis suppressing TGF-β1/Smad3 signaling pathway as well as activating Akt/eNOS signaling pathway, implicating treatment of ePLM as a promising novel non-pharmacological approach for HFpEF.
多项研究报告称，运动对射血分数保留的心力衰竭（HFpEF）有极大益处，可降低心力衰竭的住院率和死亡率。然而，运动对HFpEF的潜在机制仍不清楚。在本研究中，我们设计并构建了一种能在大鼠中进行早期被动腿部运动（ePLM）的装置，并进一步观察ePLM治疗是否对大鼠的HFpEF产生保护作用。用高盐饲料喂养大鼠以建立临床前舒张功能障碍（PDD）的动物模型，该模型最终会发展为HFpEF，然后对大鼠进行ePLM治疗。我们进行了多项实验来评估心脏和血管状况。结果表明，ePLM治疗可显著改善大鼠心脏和血管的舒张功能。我们还发现，ePLM治疗后心脏和血管的病理损伤得到改善。此外，ePLM治疗降低了心脏和血管中I型胶原蛋白、III型胶原蛋白、MMP2和MMP9的蛋白水平，表明ePLM治疗明显减轻了心脏和血管纤维化。进一步研究表明，ePLM治疗可能抑制高盐饮食诱导的HFpEF中TGF-β1/Smad3信号通路的激活，并促进Akt/eNOS信号通路的激活。总之，ePLM治疗通过抑制纤维化、抑制TGF-β1/Smad3信号通路以及激活Akt/eNOS信号通路，减轻了高盐饮食诱导的HFpEF，这表明ePLM治疗是一种有前景的新型非药物治疗HFpEF的方法。
