Huo Liqin, Zhang Jingze, Qu Zhuo, Chen Hong, Li Yuming, Gao Wenyuan
School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin 300072, China.
Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China; Department of Pharmacy, Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China.
J Ethnopharmacol. 2015 Sep 15;173:352-60. doi: 10.1016/j.jep.2015.07.048. Epub 2015 Jul 31.
Shunaoxin pill (SNX), one of the famous classical recipes in traditional Chinese medicine, is developed from the "Decoction of Xionggui". It has been used for treatment of cerebrovascular related diseases. It is well known that vasodilatation plays a very important role in cerebrovascular diseases. The effect of SNX on vasorelaxant activity has not yet been explored. Therefore, we aimed to investigate the vasorelaxant effects of SNX on isolated rat thoracic aorta so as to assess some of the possible mechanisms. We also investigate the gasotransmitter signaling pathway involved which has been rarely reported in isolated rat thoracic aorta before.
The present study was performed to examine the vasodilative activity of SNX and its mechanisms in isolated rat thoracic aorta.
SNX was studied on isolated rat thoracic aorta in vitro, including endothelium-intact and endothelium-denuded aortic rings. In present study, specific inhibitors including soluble guanylate cyclase (sGC) inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), cyclooxygenase (COX) inhibitor indomethacin (INDO), NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME), heme oxygenase-1 (HO-1) inhibitor zinc-protoporphyrin (ZnPP), cystathionine γ-lyase (CSE) inhibitor DL-Propargylglycine (PAG), non-selective K(+) channel inhibitor tetraethylammonium chloride (TEA), KV channel inhibitor 4-Aminopyridine (4-AP), and KATP channel inhibitor Glibenclamide (Gli) were used, they were added 20min before NE contraction and then added SNX to induce vasodilation.
Removal of endothelium or pretreatment of aortic rings (intact endothelium) with L-NAME, ODQ or ZnPP significantly blocked SNX-induced relaxation. Pretreatment with the non-selective K(+) channel inhibitor TEA, KV channel inhibitor 4-AP or the KATP channel inhibitor Gli, none of them had influences on the SNX-induced response (p>0.05). Besides, SNX inhibited the contraction triggered by NE in endothelium-denuded rings in Ca(2+)-free medium. SNX also produced rightward parallel displacement of CaCl2 curves.
These results suggest that SNX can induce less endothelium-dependent and more endothelium-independent vascular relaxation. The NO/cGMP and HO/CO pathways, blockade of Ca(2+) channels are inhibition of IP3R mediated Ca(2+) mobilization from intracellular stores, are likely involved in this relaxation. Furthermore, the underlying mechanisms of combined compositions in SNX await further investigations.
舒心宁片（SNX）是中医著名的经典方剂之一，由“芎归汤”化裁而来。它一直用于治疗脑血管相关疾病。众所周知，血管舒张在脑血管疾病中起着非常重要的作用。SNX对血管舒张活性的影响尚未得到研究。因此，我们旨在研究SNX对离体大鼠胸主动脉的血管舒张作用，以评估一些可能的机制。我们还研究了气体信号转导途径，此前在离体大鼠胸主动脉中很少有相关报道。
本研究旨在检测SNX在离体大鼠胸主动脉中的舒张活性及其机制。
在体外对离体大鼠胸主动脉进行SNX研究，包括内皮完整和去内皮的主动脉环。在本研究中，使用了特异性抑制剂，包括可溶性鸟苷酸环化酶（sGC）抑制剂1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ）、环氧化酶（COX）抑制剂吲哚美辛（INDO）、一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）、血红素加氧酶-1（HO-1）抑制剂锌原卟啉（ZnPP）、胱硫醚γ-裂解酶（CSE）抑制剂DL-炔丙基甘氨酸（PAG）、非选择性钾（K+）通道抑制剂氯化四乙铵（TEA）、钾离子通道（KV）抑制剂4-氨基吡啶（4-AP）和钾离子ATP通道抑制剂格列本脲（Gli），在去甲肾上腺素（NE）收缩前20分钟加入这些抑制剂，然后加入SNX诱导血管舒张。
去除内皮或用L-NAME、ODQ或ZnPP预处理主动脉环（内皮完整）可显著阻断SNX诱导的舒张。用非选择性钾（K+）通道抑制剂TEA、钾离子通道（KV）抑制剂4-AP或钾离子ATP通道抑制剂Gli预处理，均对SNX诱导的反应无影响（p>0.05）。此外，SNX在无钙培养基中抑制了去内皮环中NE引发的收缩。SNX还使氯化钙曲线向右平行移位。
这些结果表明，SNX可诱导较少的内皮依赖性和较多的非内皮依赖性血管舒张。一氧化氮/环磷酸鸟苷（NO/cGMP）和血红素加氧酶/一氧化碳（HO/CO）途径、钙（Ca2+）通道的阻断以及对肌醇三磷酸受体（IP3R）介导的细胞内钙库钙（Ca2+）动员的抑制可能参与了这种舒张。此外，SNX中复方成分的潜在机制有待进一步研究。
