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.
李新峰, 鲁光辉, 王丽斌, 李晓娟. 槲皮素对自发性高血压大鼠血管内皮功能及主动脉纤维化的影响[J]. 河北医学, 2024, 30(6): 905-912.
LI Xinfeng, LU Guanghui, et al. Effects of Quercetin on Vascular Endothelial Function and Aortic Fibrosis in Spontaneously Hypertensive Rats. HeBei Med, 2024, 30(6): 905-912.