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OACSTPCD

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 pres-sure 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 path-way and the TGF-β1/Smad3 signaling pathway.