|
|
|
| Effects of Quercetin on Vascular Endothelial Function and Aortic Fibrosis in Spontaneously Hypertensive Rats |
| LI Xinfeng, LU Guanghui, et al |
| The Second Hospital of Handan, Hebei Handan 056001, China |
|
|
|
|
Abstract Objective: To investigate the effects of quercetin on vascular endothelial function and aortic fibrosis in spontaneously hypertensive rats (SHR), and to explore its possible mechanisms.Methods: Ten Wistar-Kyoto (WKY) rats were set as the normal group; forty SHRs were randomly divided into the model group, low-dose quercetin group, high-dose quercetin group, and captopril group. The low-dose and high-dose quercetin groups were administered quercetin via gavage at doses of 50mg/kg and 100mg/kg respectively once a day, while the captopril group was given 30mg/kg captopril once a day. The normal and model groups were given an equal volume of normal saline once a day. After 8 weeks of continuous treatment, blood pressure was measured, and serum levels of endothelin-1 (ET-1), angiotensin Ⅱ (Ang-Ⅱ), thromboxane B2 (TXB2), and nitric oxide (NO) were detected by ELISA. ELISA was also used to measure the contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in the aorta. Hematoxylin and eosin (HE) staining was performed for pathological examination of the aorta, and Masson's trichrome staining was used to observe aortic fibrosis. Western blotting was conducted to detect the expression of Toll-like receptor 4 (TLR4), nuclear factor-κB p65 (NF-κB p65) in the cytoplasm and nucleus, transforming growth factor-β1 (TGF-β1), Smad3, phosphorylated Smad3 (p-Smad3), type I collagen (Col-I), and type Ⅲ collagen (Col-Ⅲ) in the aorta.Results: Compared with the model group, the low-dose quercetin group, high-dose quercetin group, and captopril group showed significantly lower systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum levels of ET-1, Ang-Ⅱ, and TXB2, along with significantly higher serum NO levels (P<0.05). The levels of TNF-α, IL-1β, and IL-6 in the aorta were significantly reduced (P<0.05). Both pathological changes and fibrosis in the aorta were significantly improved, with a notable reduction in collagen volume fraction (CVF) (P<0.05). The expression levels of TLR4, nuclear NF-κB p65, TGF-β1, p-Smad3, Col-I, and Col-Ⅲ proteins, as well as the ratios of nuclear NF-κB p65 to cytoplasmic NF-κB p65 and p-Smad3 to Smad3, were significantly lower (P<0.05). Except for SBP, DBP, and TXB2, the regulatory effects of high-dose quercetin on other indicators were superior to those of the captopril group (P<0.05).Conclusion: Quercetin can improve vascular endothelial function and reduce aortic fibrosis in SHR, lowering blood pressure. Its mechanisms may be related to the inhibition of the TLR4/NF-κB signaling pathway and the TGF-β1/Smad3 signaling pathway.
|
|
|
|
|
|
[1] 《中国心血管健康与疾病报告2022》概要[J].中国介入心脏病学杂志,2023,31(7):485-508.
[2] Wei Y,Yuan P,Zhang Q,et al.Acacetin improves endothelial dysfunction and aortic fibrosis in insulin-resistant SHR rats by estrogen receptors [J].Mol Biol Rep,2020,47(9):6899-6918.
[3] 杨忠海,李爱花,高子雅,等.卡格列净改善自发性高血压大鼠主动脉重构的作用及其机制[J].解剖学杂志,2023,46(6):468-475.
[4] 刘君,董秋梅.基于Toll样受体4/核因子κB信号通路探讨槲皮素治疗胶原诱导性关节炎模型大鼠的作用机制[J].中国医药,2022,17(6):903-907.
[5] 焦美,钟涵宇,陈克研,等.槲皮素通过TGF β1/Smad3信号通路改善慢性心衰大鼠心肌纤维化[J].解剖科学进展,2020,26(4):391-395.
[6] 余淑华,刘朏,吴倩倩,等.藏红花素对自发性高血压大鼠血管内皮功能障碍及动脉粥样硬化的作用及其ROCK/JNK信号通路机制[J].吉林大学学报(医学版),2022,48(6):1481-1489.
[7] Chen L,Wu J,Xu H,et al.Effects of tanshinone combined with valsartan on hypertensive nephropathy and its influence on renal function and vascular endothelial function [J].Am Transl Res,2021,13(5):4788-4795.
[8] Perez-Cremades D,Bueno-Beti C,Garcia-Gimenez JL,et al.Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells [J].Physiol Biochem,2023,79(2):251-260.
[9] Robinson J,Russell T,Xu Z,et al.Mechanically tunable extracellular matrix of genipin crosslinked collagen and its effect on endothelial function [J].Appl Sci (Basel),2022,12(5):2401-2412.
[10] 陈向军,顾兴,王在强,等.颗粒酶B激活TGF-β1/Smad3通路促进博来霉素导致的肺纤维化[J].中华肺部疾病杂志(电子版),2023,16(5):630-634. |
|
|
|
2024, Vol. 30 
