土茯苓总黄酮改善ISO诱导的小鼠心肌肥大和心脏炎症的机制研究
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浙江省中医药研究院

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浙江省自然科学基金资助项目;浙江省科技厅2024年院所专项


Mechanism of Smilax glabra Roxb. flavonoids ameliorating ISO-induced cardiac hypertrophy and cardiac inflammation in mice
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Zhejiang Academy of Traditional Chinese Medicine

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Zhejiang Provincial Natural Science Foundation of China under Grant;institute Specifical Foundation for Zhejiang Provincial Department of Science and Technology

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    摘要:

    【】目的 研究土茯苓总黄酮(SGF)对异丙肾上腺素(ISO)诱导的小鼠心肌肥大和心脏炎症的作用及机制。方法 C57/6J小鼠随机分为正常组、ISO模型组(1.25mg/kg.d)、SGF低剂量组(50mg/kg.d)、SGF高剂量组(100mg/kg.d),SGF给药组均在造模前预防给药7天,之后各组进行ISO皮下注射,连续注射7天后进行超声心动图测定;眼眶取血分离血清,检测血中NT-proBNP及炎症因子IL-1β、IL-6、TNF-α含量;收集心肌标本,观察心肌组织的病理学改变,DHE染色检测心肌ROS水平,检测心脏相关肥大基因mRNA水平变化以及NLRP3/Caspase-1/IL-18炎症级联通路上关键因子蛋白水平表达的变化。结果 SGF预防给药可降低超声心动图中的IVSd、IVSs和EF,提高LVIDs、LVIDd和ESV,降低血中IL-1β、IL-6、TNF-α和NT-proBNP含量,抑制心脏相关肥大基因ANP、BNP、β-MHC mRNA表达水平上调,抑制心肌ROS水平增加,下调NLRP3/Caspase-1/IL-18炎症级联通路上关键因子NLRP3、Caspase-1(p20)和IL-18的蛋白表达,改善心肌细胞肥大和排列紊乱的情况,减少心肌纤维外的成纤维细胞增多,减轻炎症细胞浸润和心肌组织纤维化情况。结论 SGF可改善ISO诱导的小鼠心肌肥大和心脏炎症,可能通过NLRP3/Caspase-1/IL-18炎症级联通路起作用。

    Abstract:

    【】Objective To study the effect and mechanism of Smilax glabra Roxb. flavonoids (SGF) on myocardial hypertrophy and cardiac inflammation induced by isoproterenol (ISO) in mice. Methods C57/6J mice were randomly divided into normal group, ISO model group (1.25mg/kg.d), SGF low-dose group (50mg/kg.d) and SGF high-dose group (100mg/kg.d). SGF administration groups were given prophylactic administration for 7 days before modeling, and then ISO subcutaneous injection was performed in each group, and echocardiography was performed after continuous injection for 7 days; Serum was separated from orbital blood, and the contents of NT-proBNP and inflammatory factors IL-1β, IL-6 and TNF-α in blood were detected. Myocardial specimens were collected and the pathological changes of myocardial tissue were observed, the myocardial ROS levels were detected by DHE staining. And the mRNA levels of heart-related hypertrophy genes and the changes in the expression of key factor proteins in the inflammatory grade pathway of NLRP3/Caspase-1/IL-18 were detected in myocardial tissue. Results SGF prophylactic administration decreased IVSd, IVSs, and EF in echocardiography and increased LVIDs, LVIDd, and ESV. The contents of IL-1β, IL-6, TNF-α and NT-proBNP in blood were decreased, and the mRNA expression levels of heart-related hypertrophy genes ANP, BNP and β-MHC were inhibited. The increase of myocardial ROS level was inhibited. The protein expression of NLRP3, Caspase-1(p20) and IL-18, which are key factors in the NLRP3/Caspase-1/IL-18 inflammatory pathway, was down-regulated in myocardial tissue. The hypertrophy and disordered arrangement of cardiomyocytes were improved, the increase of fibroblasts outside myocardial fibers was reduced, and the infiltration of inflammatory cells and fibrosis of myocardial tissue were alleviated. Conclusion SGF can improve ISO-induced myocardial hypertrophy and cardiac inflammation in mice, which may act through the NLRP3/Caspase-1/IL-18 inflammatory grade pathway.

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  • 收稿日期:2024-03-12
  • 最后修改日期:2024-04-14
  • 录用日期:2024-08-14
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