荷叶碱通过调节自发性高血压大鼠多种信号通路改善高血压血管重构。
Neferine ameliorates hypertensive vascular remodeling modulating multiple signaling pathways in spontaneously hypertensive rats.
机构信息
Department of Orthopaedics, Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350000, China; Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian 350122, China.
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian 350122, China.
出版信息
Biomed Pharmacother. 2023 Feb;158:114203. doi: 10.1016/j.biopha.2022.114203. Epub 2023 Jan 4.
BACKGROUND
Neferine exhibits therapeutic effects on anti-hypertension. However, the effect of neferine on hypertensive vascular remodeling remains unexplored. Therefore, the current study was to investigate the effect of neferine on hypertensive vascular remodeling and its underlying mechanisms.
METHODS
Total 30 male spontaneously hypertensive rats (SHRs) were divided randomly into five groups, including SHR, Neferine-L (2.5 mg/kg/day), Neferine-M (5 mg/kg/day), Neferine-H (10 mg/kg/day), and Valsartan (10 mg/kg/day) groups (n = 6 for each group). Wistar Kyoto (WKY) rats were set as control group (n = 6). Noninvasive blood pressure system, ultrasound, hematoxylin and eosin staining, masson trichrome staining were used to detect the blood pressure, pulse wave velocity (PWV), pathological changes and collagen content in abdominal aortas of SHRs. RNA-sequencing and immunohistochemistry(IHC) analyses were used to identify and verify the differentially expressed transcripts and activation of associated signaling pathways in SHRs.
RESULTS
Various concentrations of neferine or valsartan treatment substantially reduced the elevation of blood pressure, PWV, and abdominal aortic thickening of SHRs. RNA-sequencing and KEGG analyses recognized 441 differentially expressed transcripts and several enriched pathways (including PI3K/AKT and TGF-β/Smad2/3 signaling pathways) after neferine treatment. Masson trichromatic staining and IHC analysis demonstrated that neferine treatment decreased the collagen content and down-regulated the protein expression of PCNA, collagen I & III, and fibronectin, as well as p-PI3K, p-AKT, TGF-β1 and p-Smad2/3 in abdominal aortic tissues of SHRs.
CONCLUSION
Neferine treatment exhibits therapeutic effects on anti-hypertension and reduces vascular remodeling, as well as suppresses the abnormal activation of multiple signaling pathways, including PI3K/AKT and TGF-β1/Smad2/3 pathways.
背景
小檗碱对高血压有治疗作用。然而，小檗碱对高血压血管重构的影响尚不清楚。因此，本研究旨在探讨小檗碱对高血压血管重构的影响及其作用机制。
方法
将 30 只雄性自发性高血压大鼠（SHRs）随机分为 5 组，包括 SHR 组、小檗碱低剂量（2.5mg/kg/天）组、小檗碱中剂量（5mg/kg/天）组、小檗碱高剂量（10mg/kg/天）组和缬沙坦（10mg/kg/天）组（每组 6 只）。Wistar Kyoto（WKY）大鼠设为对照组（n=6）。采用无创血压系统、超声、苏木精-伊红（HE）染色、Masson 三色染色检测 SHRs 的血压、脉搏波速度（PWV）、腹主动脉病理变化和胶原含量。RNA 测序和免疫组织化学（IHC）分析用于鉴定和验证 SHRs 中差异表达的转录本和相关信号通路的激活。
结果
不同浓度的小檗碱或缬沙坦治疗可显著降低 SHRs 的血压升高、PWV 升高和腹主动脉增厚。RNA 测序和 KEGG 分析鉴定了小檗碱处理后 441 个差异表达的转录本和几个富集的通路（包括 PI3K/AKT 和 TGF-β/Smad2/3 信号通路）。Masson 三色染色和 IHC 分析表明，小檗碱治疗可降低 SHRs 腹主动脉组织中的胶原含量，下调 PCNA、胶原 I 和 III、纤维连接蛋白以及 p-PI3K、p-AKT、TGF-β1 和 p-Smad2/3 的蛋白表达。
结论
小檗碱治疗具有抗高血压作用，可减轻血管重构，并抑制包括 PI3K/AKT 和 TGF-β1/Smad2/3 通路在内的多种信号通路的异常激活。
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