An herbal preparation ameliorates heart failure with preserved ejection fraction by alleviating microvascular endothelial inflammation and activating NO-cGMP-PKG pathway
An herbal preparation ameliorates heart failure with preserved ejection fraction by alleviating microvascular endothelial inflammation and activating NO-cGMP-PKG pathway
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一种草药制剂通过减轻微血管内皮炎症和激活 NO-cGMP-PKG 通路来改善射血分数保留的心力衰竭
DOI：
10.1016/j.phymed.2021.153633
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发表时间：
2021-07-25
期刊：
影响因子：
7.9
通讯作者：
Fan, Guanwei
中科院分区：
文献类型：
--
作者：
Huang, Yuting;Zhang, Kai;Fan, Guanwei
背景：射血分数保留性心力衰竭（HFpEF）是一种异质性疾病，给临床医生带来了巨大的挑战。目前，没有安全有效的HFpEF治疗。在这项研究中，我们报告了一个标准化的草药产品，芪参益气（QSYQ），可用于治疗HFpEF.Methods：HFpEF小鼠建立的组合N-ω-硝基-L-精氨酸甲酯（L-NAME），并喂养高脂饲料14周。在第10周，HFpEF小鼠经口灌胃给予达格列净或QSYQ，持续4周。评价HFpEF小鼠的血压、超声心动图、血流动力学、白细胞浸润和氧化应激。此外，炎症因子，内皮细胞粘附因子，内皮细胞间质转化（EndMT）marker进行了investigated.Results：QSYQ显着减弱向心性心脏重构，同时改善舒张功能和左心室顺应性在HFpEF小鼠。QSYQ还抑制HFpEF期间的炎症和免疫细胞募集。QSYQ处理小鼠心肌中CD 8（+）、CD 4（+）T细胞和CD 11b/c+单核细胞的浸润显著减轻。TNF-α、MCP-1、NF-κ B和NLRP 3水平在QSYQ治疗后也降低。此外，QSYQ显着逆转内皮细胞粘附因子的表达和EndMT的发生。结论：QSYQ通过抑制微血管内皮炎症和激活NO-cGMP-PKG通路，改善HFpEF心肌组织中eNOS解偶联，从而改善HFpEF。
Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disease presenting a substantial challenge to clinicians. Currently, there is no safe and efficacious HFpEF treatment. In this study, we reported a standardized herbal medicinal product, QiShenYiQi (QSYQ), that can be used in the treatment of HFpEF.Methods: HFpEF mice were established by infusing a combination of N-omega-nitro-L-arginine methyl ester (L-NAME) and feeding them a high-fat diet for 14 weeks. In the 10th week, the HFpEF mice were given dapagliflozin or QSYQ via oral gavage for four weeks. The blood pressure, echocardiography, hemodynamics, leukocyte infiltration, and oxidative stress in HFpEF mice were evaluated. Besides, inflammatory factors, endothelial adhesion factors, and endothelial-mesenchymal transformation (EndMT) markers were investigated.Results: QSYQ significantly attenuated concentric cardiac remodeling while improving diastolic function and left ventricular compliance in HFpEF mice. QSYQ also inhibited inflammation and immunocyte recruitment during HFpEF. The infiltration of CD8(+), CD4(+) T cells, and CD11b/c+ monocytes was substantially mitigated in the myocardium of QSYQ-treated mice. TNF-alpha, MCP-1, NF-kappa B, and NLRP3 levels also reduced after QSYQ treatment. Furthermore, QSYQ significantly reversed the elevated expression of endothelial adhesion factors and EndMT occurrence. These effects of QSYQ were demonstrated by the activation of NO-cGMP-PKG pathway and reduction of eNOS uncoupling in the HFpEF heart.Conclusion: These results provide novel evidence that QSYQ treatment improves HFpEF by inhibiting microvascular endothelial inflammation and activating NO-cGMP-PKG pathway.