Chen Ya-Juan, Wang Lei, Zhou Guang-Yu, Yu Xian-Lun, Zhang Yong-Hui, Hu Na, Li Qing-Qing, Chen Chen, Qing Chen, Liu Ying-Ting, Yang Wei-Min
School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
Zhaotong Institute of Tianma, Zhaotong 657000, China.
Chin J Nat Med. 2015 Apr;13(4):264-73. doi: 10.1016/S1875-5364(15)30013-3.
Scutellarin (SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we investigated the vasoprotective effects of SCU against HR-induced endothelial dysfunction (ED) in isolated rat CA and the possible mechanisms involving cyclic guanosine monophosphate (cGMP) dependent protein kinase (PKG). The isolated endothelium-intact and endothelium-denuded rat CA rings were treated with HR injury. Evaluation of endothelium-dependent and -independent vasodilation relaxation of the CA rings were performed using wire myography and the protein expressions were assayed by Western blotting. SCU (10-1 000 μmol·L(-1)) could relax the endothelium-intact CA rings but not endothelium-denuded ones. In the intact CA rings, the PKG inhibitor, Rp-8-Br-cGMPS (PKGI-rp, 4 μmol·L(-1)), significantly blocked SCU (10-1 000 μmol·L(-1))-induced relaxation. The NO synthase (NOS) inhibitor, NO-nitro-L-arginine methylester (L-NAME, 100 μmol·L(-1)), did not significantly change the effects of SCU (10-1 000 μmol·L(-1)). HR treatment significantly impaired ACh-induced relaxation, which was reversed by pre-incubation with SCU (500 μmol·L(-1)), while HR treatment did not altered NTG-induced vasodilation. PKGI-rp (4 μmol·L(-1)) blocked the protective effects of SCU in HR-treated CA rings. Additionally, HR treatment reduced phosphorylated vasodilator-stimulated phosphoprotein (p-VASP, phosphorylated product of PKG), which was reversed by SCU pre-incubation, suggesting that SCU activated PKG phosphorylation against HR injury. SCU induces CA vasodilation in an endothelium-dependent manner to and repairs HR-induced impairment via activation of PKG signaling pathway.
灯盏花素（SCU），一种来自传统中药植物的黄酮类化合物。我们之前的研究表明，SCU主要以内皮依赖性方式舒张小鼠主动脉。在本研究中，我们研究了SCU对离体大鼠颈总动脉（CA）中过氧化氢（HR）诱导的内皮功能障碍（ED）的血管保护作用以及涉及环磷酸鸟苷（cGMP）依赖性蛋白激酶（PKG）的可能机制。将离体的完整内皮和去内皮大鼠CA环用HR损伤处理。使用线肌张力测定法评估CA环的内皮依赖性和非内皮依赖性血管舒张，并用蛋白质印迹法测定蛋白质表达。SCU（10 - 1000 μmol·L⁻¹）可舒张完整内皮的CA环，但不能舒张去内皮的CA环。在完整的CA环中，PKG抑制剂Rp - 8 - Br - cGMPS（PKGI - rp，4 μmol·L⁻¹）显著阻断SCU（10 - 1000 μmol·L⁻¹）诱导的舒张。一氧化氮合酶（NOS）抑制剂NO - 硝基 - L - 精氨酸甲酯（L - NAME，100 μmol·L⁻¹）未显著改变SCU（10 - 1000 μmol·L⁻¹）的作用。HR处理显著损害乙酰胆碱（ACh）诱导的舒张，预先用SCU（500 μmol·L⁻¹）孵育可逆转该作用，而HR处理未改变硝酸甘油（NTG）诱导的血管舒张。PKGI - rp（4 μmol·L⁻¹）阻断了SCU对HR处理的CA环的保护作用。此外，HR处理降低了磷酸化的血管舒张刺激磷蛋白（p - VASP，PKG的磷酸化产物），预先用SCU孵育可逆转该作用, 表明SCU激活PKG磷酸化以对抗HR损伤。SCU以内皮依赖性方式诱导CA血管舒张，并通过激活PKG信号通路修复HR诱导的损伤。
