<br>心舒宝片通过调节 THBD/ARRB1/FGF1/STIM1 信号对射血分数降低的心力衰竭的心脏保护作用,Biomedicine & Pharmacotherapy

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心舒宝片通过调节 THBD/ARRB1/FGF1/STIM1 信号对射血分数降低的心力衰竭的心脏保护作用
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2023-07-07 , DOI: 10.1016/j.biopha.2023.115119
Fengrong Zhang ₁ , Xingyue Xu ₂ , Jinli Hou ₂ , Honghe Xiao ₂ , Feifei Guo ₃ , Xianyu Li ₂ , Hongjun Yang ₄

Affiliation

中医药治疗心力衰竭（HF）的早中期在缓解和预防方面具有独特的优势。本研究的目的是评估心舒宝（XSB）在诱发小鼠心肌梗死（MI）后心衰不同阶段的体内治疗效果，并使用基于质谱的蛋白质组学来识别潜在的治疗靶点根据 XSB 治疗后的分子变化，针对 HF 的不同阶段。 XSB 在射血分数降低的 HF 前期 (HFrEF) 阶段具有较高的心脏保护作用，但在 HFrEF 阶段的作用较弱或没有作用。超声心动图测量结果支持了这一点，显示 XSB 降低了心力衰竭的射血分数和缩短分数。 XSB 给药改善了 HFrEF 小鼠模型前后的心脏功能，改善了心肌细胞形态和亚细胞结构的有害变化，并减少了心脏纤维化。蛋白质组学分析表明，当给小鼠施用 8 周和 6 周时，XSB 干预专门针对血栓调节蛋白 (THBD) 和基质相互作用分子 1 (STIM1) 蛋白。此外，MI 诱导后 8、6 和 4 周的 XSB 干预增加了成纤维细胞生长因子 1 (FGF1) 的表达并减少了抑制蛋白 β1 (ARRB1)，这分别是心脏成纤维细胞转化和胶原合成的经典生物标志物。总体而言，该研究表明 XSB 的早期干预可能是预防 HFrEF 的有效策略，并强调了进一步研究 HFrEF 补救策略的潜在治疗目标。

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Cardioprotective efficacy of Xin-shu-bao tablet in heart failure with reduced ejection fraction by modulating THBD/ARRB1/FGF1/STIM1 signaling

Traditional Chinese medicine offer unique advantages in mitigating and preventing early or intermediate stage for treating heart failure (HF). The purpose of this study was to assess the in vivo therapeutic efficacy of Xin-shu-bao (XSB) at different stages of HF following induction of a myocardial infarction (MI) in mice and use mass spectrometry-based proteomics to identify potential therapeutic targets for different stages of HF based on the molecular changes following XSB treatment. XSB had high cardioprotective efficacy in the pre-HF with reduced ejection fraction (HFrEF) stages, but had a weak or no effect in the post-HFrEF stages. This was supported by echocardiographic measurements showing that XSB decreased ejection fraction and fractional shortening in HF. XSB administration improved cardiac function in the pre- and post-HFrEF mouse model, ameliorated deleterious changes to the morphology and subcellular structure of cardiomyocytes, and reduced cardiac fibrosis. Proteomics analysis showed that XSB intervention exclusively targeted thrombomodulin (THBD) and stromal interaction molecule 1 (STIM1) proteins when administered to the mice for both 8 and 6 weeks. Furthermore, XSB intervention for 8, 6, and 4 weeks after MI induction increased the expression of fibroblast growth factor 1 (FGF1) and decreased arrestin β1 (ARRB1), which are classic biomarkers of cardiac fibroblast transformation and collagen synthesis, respectively. Overall, the study suggests that early intervention with XSB could be an effective strategy for preventing HFrEF and highlights potential therapeutic targets for further investigation into HFrEF remediation strategies.

更新日期：2023-07-07

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