圣草酚改善自发性高血压大鼠血管重构的机制研究

Eriodictyol resists vascular remodeling in spontaneously hypertensive rats by inhibiting TLR4/NF-κB signaling

目的:观察圣草酚能否改善自发性高血压大鼠(SHRs)的血管重构,并探讨其可能机制。方法:设置WKY正常对照、SHRs模型及圣草酚给药(EDT 120 mg/kg,SHRs+EDT)组,连续给药20周。尾袖法测量血压[收缩压(SBP)、舒张压(DBP)及平均血压(MBP)],超声检测脉搏波速度(PWV),HE染色观察主动脉中膜厚度(MT),MASSON染色观察主动脉胶原百分比(VFC)变化,ELISA检测血清TNF-α、IL-6及IL-10含量,q-PCR检测主动脉中TNF-α、IL-6及IL-10 mRNA变化,免疫组化观察主动脉CollagenⅠ和CollagenⅢ表达,Western blotting检测主动脉TGF-β1、MMP-2、MMP-9、Toll样受体4(TLR4)、p-IкBa、IкBa、p-p65及p65表达。结果:圣草酚给药20周后,SHRs的SBP、DBP、MBP及PWV显著下降(P<0.05或P<0.01),主动脉的MT和VFC显著减少(P<0.05),CollagenⅠ、CollagenⅢ、TGF-β1、MMP-2、MMP-9、TLR4、p-IкBa、p-p65蛋白表达显著减少(P<0.05或P<0.01)。结论:圣草酚长期给药后,可抑制TLR4、NF-κB表达发挥抗炎作用,从而减少TGF-β1、MMP-2、MMP-9表达,使胶原含量下降,改善SHRs的主动脉重构和硬化。

AIM:To observe the vascular remodeling of eriodictyol(EDT)in spontaneously hypertensive rats(SHRs)by inhibiting TLR4/NF-kB signaling and to investigate the potential mechanism of action.METHODS:WKY normal control,SHRs model and EDT administration(EDT 120 mg/kg,SHRs+EDT)group were set for 20 weeks.Tail cuff method for blood BP measurement(SBP,DBP and MBP).Ultrasonic detection of pulse wave velocity(PWV).The aortic media membrane thickness(MT)was visualized by HE staining.The percentage of aortic collagen(VFC)changes were observed by MASSON staining,Serum content of TNF-α,IL-6,and IL-10 was measured by ELISA.The TNF-α,IL-6,and IL-10 mRNA changes in the aorta were detected by q-PCR.The aortic Collagen I and CollagenⅢexpression was observed by immunohistochemistry,WB measured the expression of aortic TGF-β1,MMP-2,MMP-9,TLR4,p-IкBa,IкBa,p-p65 and p65.RESULTS:After 20 weeks of EDT administration,SBP,DBP,MBP and PWV of SHRs were significantly decreased,MT and VFC of aorta were significantly decreased,and protein expressions of CollagenⅠ,CollagenⅢ,TGF-β1,MMP-2,MMP-9,TLR4,p-I Camba and p-p65 were significantly decreased.CONCLUSION:After long-term administration of EDT could inhibit TLR4/NF-κB signaling and exert anti-inflammatory effects,thus reducing TGF-β1,MMP-2 and MMP-9 expression,decreasing collagen content,and finally improving aortic remodeling and sclerosis of SHRs.