兔子皮下注射 BNP:缓解心房颤动心肌重塑的新方法

Si Zhong, Rui He, Jia Yu, Hongyan Zhao
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摘要

背景:心房颤动(AF)是一种常见的心律失常,与发病率和死亡率的增加有关,因此需要新的治疗策略。本研究旨在评估 B 型钠尿肽(BNP)对兔房颤模型心脏结构重塑的影响:对兔子进行快速起搏以诱导房颤模型,并以 20 μg/kg/d 的剂量皮下注射 BNP,每天两次,连续三周。电生理学测量评估房颤诱导率和心房有效折返期(AERP),超声心动图测量评估左心房的大小和功能。组织学检查包括苏木精和伊红(H&E)染色以及马森三色染色,以观察心肌组织结构和纤维化情况。使用透射电子显微镜观察心肌组织的超微结构:研究发现,BNP 治疗可显著降低房颤诱发率(p < 0.001),改善 AERP(p < 0.001),改善左心房的结构和功能变化(p < 0.05)。组织学分析表明,BNP 治疗后心肌纤维化减少(p < 0.05)。结果还显示,BNP 可减轻房颤引起的心肌细胞重塑,对转化生长因子-β 1 (TGF-β1)、基质金属蛋白酶组织抑制剂 1 (TIMP1)、基质金属蛋白酶 9 (MMP9) 和胶原 I/III 的表达水平有显著影响(p < 0.05):这些研究结果表明,皮下注射 BNP 可作为一种有效的治疗药物,缓解房颤患者的心脏结构重塑,对治疗房颤具有重要的临床意义。
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Subcutaneous BNP Injections in Rabbits: A Novel Approach to Mitigate Myocardial Remodeling in Atrial Fibrillation.

Background: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with increased morbidity and mortality, highlighting the need for novel therapeutic strategies. This study aimed to evaluate the effects of B-type natriuretic peptide (BNP) on cardiac structural remodeling in a rabbit model of AF.

Methods: Rabbits were subjected to rapid pacing to induce an AF model, and BNP was delivered subcutaneously at a dose of 20 μg/kg/d twice per day for three weeks. Electrophysiological measurements were taken to assess the AF induction rate and atrial effective refractory period (AERP), while echocardiographic measurements evaluated left atrial size and function. Histological examinations included hematoxylin and eosin (H&E) staining and Masson's trichrome staining to observe myocardial tissue structure and fibrosis. The ultrastructure of myocardial tissue was observed using a transmission electron microscope.

Results: The study found that BNP treatment significantly reduced the AF induction rate (p < 0.001), improved AERP (p < 0.001), and ameliorated structural and functional changes in the left atrial (p < 0.05). Histological analysis demonstrated decreased myocardial fibrosis post-BNP treatment (p < 0.05). Results also showed that BNP attenuated the cardiomyocyte remodeling caused by AF, as evidenced by significant effects on the expression levels of transforming growth factor-β 1 (TGF-β1), tissue inhibitors of matrix metalloproteinases 1 (TIMP1), matrix metalloproteinase 9 (MMP9), and Collagen I/III (p < 0.05).

Conclusion: These findings suggest that subcutaneous injections of BNP may serve as an effective therapeutic agent in mitigating cardiac structural remodeling in AF, offering significant clinical implications for treating this condition.

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