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秋水仙碱可减轻射血分数保留心力衰竭大鼠的炎症并改善舒张功能障碍。

Colchicine alleviates inflammation and improves diastolic dysfunction in heart failure rats with preserved ejection fraction.

机构信息

Department of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, PR China.

Department of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, PR China.

出版信息

Eur J Pharmacol. 2022 Aug 15;929:175126. doi: 10.1016/j.ejphar.2022.175126. Epub 2022 Jun 30.

Abstract

PURPOSE

Several studies have reported that colchicine attenuates cardiac inflammation and improves cardiac function in myocardial infarction and atrial fibrillation. However, no study has investigated its effect on heart failure with preserved ejection fraction (HFpEF). Hence, this study aimed to assess its efficacy in a high salt diet (HSD)-induced HFpEF rat model.

METHODS

A rat hypertension-induced HFpEF model was created by treating Dahl/SS salt-sensitive rats with an HSD for 6 weeks. Colchicine was given via gavage daily as treatment. Cardiac function and inflammation were assessed using echocardiography, histology, and ELISA. Furthermore, the expression levels of NLRP3 and NF-κB signaling pathways were examined.

RESULTS

Treatment with colchicine increased survival and attenuated cardiac dysfunction, as indicated by decreased echocardiographic E/A ratio and longer exercise endurance along with reduced ventricular fibrosis and remodeling in HSD-induced Dahl rats. The treatment also reduced cardiac oxidative stress and inflammatory cell infiltration, as inferred from lower mRNA expressions of TNFα and CCL2 as well as protein expressions of NLRP3 and NF-κB pathways.

CONCLUSION

The findings signify that colchicine plays a crucial role in alleviating systemic inflammation and NLRP3 inflammation activation as well as in attenuating cardiac dysfunction and fibrosis in HSD-induced HFpEF model. Colchicine, therefore, holds therapeutic potential for further clinical applications.

摘要

目的

几项研究报告称,秋水仙碱可减轻心肌梗死和心房颤动中的心肌炎症并改善心功能。然而,尚无研究探讨其对射血分数保留型心力衰竭(HFpEF)的影响。因此,本研究旨在评估其在高盐饮食(HSD)诱导的 HFpEF 大鼠模型中的疗效。

方法

通过用 HSD 处理 Dahl/SS 盐敏感大鼠 6 周,创建大鼠高血压诱导的 HFpEF 模型。通过灌胃每天给予秋水仙碱进行治疗。使用超声心动图、组织学和 ELISA 评估心脏功能和炎症。此外,还检查了 NLRP3 和 NF-κB 信号通路的表达水平。

结果

秋水仙碱治疗可提高存活率,并减轻 HSD 诱导的 Dahl 大鼠的心脏功能障碍,表现为超声心动图 E/A 比值降低,运动耐力延长,心室纤维化和重构减少。该治疗还减轻了心脏氧化应激和炎症细胞浸润,这可以从 TNFα 和 CCL2 的 mRNA 表达以及 NLRP3 和 NF-κB 通路的蛋白表达降低推断出来。

结论

这些发现表明,秋水仙碱在减轻全身炎症和 NLRP3 炎症激活以及减轻 HSD 诱导的 HFpEF 模型中心脏功能障碍和纤维化方面起着至关重要的作用。因此,秋水仙碱具有进一步临床应用的治疗潜力。

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