| 黄连解毒汤通过Notch1/NF-κB信号通路改善大鼠高血压性心肌肥厚 |
| 投稿时间：2023-12-23 修订日期：2024-03-07 点此下载全文 |
| 引用本文：鲁子瑜,李健英,蒋碧辉,魏明慧,尹东杰,任中杰,薛明明.黄连解毒汤通过Notch1/NF-κB信号通路改善大鼠高血压性心肌肥厚[J].医学研究杂志,2025,54(2):123-131 |
| DOI：
10.11969/j.issn.1673-548X.2025.02.020 |
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| 基金项目:内蒙古自治区卫生健康科技计划项目(202201221)；内蒙古自治区自然科学基金资助项目(2022LHMS08002) |
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| 中文摘要:目的 探讨黄连解毒汤(huangian jiedu decoction, HLJDD)对高血压性心肌肥厚大鼠(hypertensive cardiac hypertrophy, HCH)的保护机制。方法 通过腹主动脉缩窄术(abdominal aortic coarctation, AAC)诱导SD大鼠构建HCH模型。将SD大鼠通过简单随机抽样法随机分为假手术(Sham)组、模型(Mod)组、模型+HLJDD高、中、低剂量(Mod+H、Mod+M、Mod+L)组、Mod+卡托普利(Cap)组,检测血压、超声心动图、苏木精-伊红染色及Masson染色,探讨HLJDD改善大鼠HCH的作用。根据前述实验结果,再将SD大鼠通过简单随机抽样法随机分为Sham组、Mod组、模型+Notch1抑制剂(DAPT)组、模型+Notch1激动剂(Jagged-1)组、模型+HLJDD高剂量(HLJDD)组、模型+HLJDD高剂量+Notch1抑制剂(DAPT+H)组、模型+HLJDD高剂量+Notch1激动剂(Jagged-1+H)组,观察苏木精-伊红染色及Masson染色,实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction, RT-qPCR)与Western blot法检测相关炎性细胞因子的表达水平,进一步探究HLJDD的作用机制。结果 与Mod组比较,Mod+H组大鼠血压降低(P<0.05),心功能提高(P<0.05),心肌损伤缓解及心肌纤维化降低(P<0.05)。与Mod组比较,DAPT组心肌损伤和纤维化加剧,Notch1、Hes1表达水平降低(P<0.05),炎性细胞因子及NF-κB p65表达水平增高(P<0.05),Jagged-1组和HLJDD组与之相反；与HLJDD组比较,DAPT+H组心肌损伤和纤维化加剧,Notch1、Hes1表达水平降低(P分别为<0.05、<0.01),炎性细胞因子及NF-κB p65表达水平增高(P<0.05),Jagged-1+H组与其相反,说明HLJDD可以激活Notch1信号通路并抑制NF-κB信号通路和炎性细胞因子的释放。结论 HLJDD可以减轻AAC诱导的大鼠HCH,其机制可能是通过影响Notch1/NF-κB信号通路实现的,且Notch1信号通路与NF-κB信号通路存在一定的负反馈调节关系。 |
| 中文关键词:黄连解毒汤 高血压性心肌肥厚 Notch1信号通路 NF-κB信号通路 |
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| Huanglian Jiedu Decoction Improves Hypertensive Cardiac Hypertrophy in Rats Through the Notch1/NF-κB Signaling Pathway. |
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| Abstract:Objective To investigate the protective mechanisms of huanglian jiedu decoction (HLJDD) against hypertensive cardiac hypertrophy (HCH) in rats. Methods The HCH model was constructed in SD rats through abdominal aortic constriction (AAC). Rats were randomly divided into the sham operation (Sham) group, model (Mod) group, Mod+HLJDD high, medium and low-dose (Mod+H, Mod+M, Mod+L) groups, and Mod+Captopril (Cap) group using a simple random sampling method. Blood pressure, echocardiography, hematoxylin-eosin staining, and Masson staining were performed to assess the impact of HLJDD on HCH. Based on the results of part one, rats were further randomly divided into Sham group, Mod group, Mod+Notch1 inhibitor (DAPT) group, Mod+Notch1 agonist (Jagged-1) group, Mod+HLJDD high-dose (HLJDD) group, Mod+HLJDD high-dose+Notch1 inhibitor (DAPT+H) group, and Mod+HLJDD high-dose+Notch1 agonist (Jagged-1+H) group using a simple random sampling method. Hematoxylin-eosin staining and Masson staining were observed. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the expression levels of related inflammatory factors, to further explore the mechanisms of HLJDD. Results Compared with the Mod group, rats in the Mod+H group exhibited reduced blood pressure (P<0.05), improved cardiac function (P<0.05), relieved myocardial injury and decreased myocardial fibrosis (P<0.05). Compared with the Mod group, the DAPT group displayed aggravated myocardial injury and fibrosis, decreased expression levels of Notch1 and Hes1 (P<0.05), and increased expression levels of inflammatory factors and NF-κB p65 (P<0.05). The Jagged-1group and HLJDD group showed opposite results. Compared with HLJDD group, the DAPT+H group displayed aggravated myocardial injury and fibrosis, decreased expression levels of Notch1 and Hes1 (P<0.05, P<0.01), and increased expression levels of inflammatory factors and NF-κB p65 (P<0.05). The Jagged-1+H group showed opposite results, indicating that HLJDD can partially activate the Notch1signaling pathway while inhibiting the NF-κB signaling pathway and the release of inflammatory factors. Conclusion HLJDD can alleviate AAC-induced HCC in rats, and its mechanism may be achieved through the modulation of the Notch1/NF-κB signaling pathway. Additionally, a certain negative feedback regulatory relationship exists between the Notch1signaling pathway and the NF-κB signaling pathway. |
| keywords:Huanglian jiedu decoction Hypertensive cardiac hypertrophy Notch1signaling pathway NF-κB signaling pathway |
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