黄芩素对大鼠离体胸主动脉的舒张作用及其机制

目的:研究黄芩素(BAI)对去甲肾上腺素(NE,1×10-6mol· L-1)和氯化钾(KCl,6×10-2 mol·L-1)预收缩健康成年雄性大鼠胸主动脉环的舒张作用,并探讨其作用机制.方法:应用离体血管环技术观察BAI对大鼠胸主动脉环张力的作用,记录NE预收缩的离体大鼠胸主动脉环张力变化.采用一氧化氮合酶(eNOS)抑制剂L-硝基精氨酸甲酯(L-NAME,1×10-4mol·L-1)、环氧合酶抑制剂吲哚美辛(INDO,1×10-5mol· L-1)和鸟苷酸环化酶抑制剂亚甲蓝(MB,1×10-5mol· L-1)和不同的钾通道阻滞剂预孵后观察BAI对血管环张力改变的影响,并观察对NE诱发的内钙释放和CaCl2引起的外钙内流的影响.结果:BAI对NE或KCl预收缩的内皮完整和去内皮大鼠离体胸主动脉环均产生明显的舒张作用,与溶剂组相比差异有统计学意义.预先用L-NAME,MB,KV通道阻断剂四氨基吡啶(4-AP,1×10-4mol· L-1),KC.通道阻断剂四乙胺(TEA,1×10-3mol· L-1),Kir通道阻断剂氯化钡(BaCl2,1×10-4mol·L-1)孵育后,BAI对预收缩的血管张力的改变与无阻断药时比较,差异均无统计学意义；预先用KATP通道阻断剂格列苯脲(Gli,1×10-5mol·L-1)和INDO孵育后,BAI的舒张血管作用减弱,与无阻断药比较差异有统计学意义(P＜0.05)；且BAI对NE外钙内流引起的收缩有明显的抑制作用.结论:黄芩素可明显降低由NE诱发的血管环张力的升高,且其作用具有浓度依赖性,此作用有内皮依赖性和非内皮依赖性的特点.内皮依赖性收缩可能与前列环素(PGI2)途径有关,非内皮依赖机制与KATP通道和钙离子通道有关.

Vasodilatation Effect of Baicalein on Rat Thoracic Artery and its Related Mechanism

Objective: To observe vasodilation effect of baicalein (BAI) and its mechanism. Method: Isotonic tension was recorded in isolated rat thoracic artery induced by norepinephrine(NE,1×10^-6mol·L^-1) and KCl(6×10^-2mol·L^-1). To investigate the vasodilation effect of BAI and the influence of various drugs on it were observed in the rings with endothelium intact or endothelium denuded. Result: BAI was shown to significantly relax the endothelium-intact arteries induced by NE and KCl, relaxation had fall down on endothelium-denuded arteries. NG-nitro-L-argininemethylester (L-NAME,1×10^-4mol·L^-1), methylene blue (MB,1×10^-5mol·L^-1), tetrathylamonium(TEA,1×10^-3mol·L^-1), 4-aminopyridine (4-AP,1×10^-4mol·L^-1), BaCl₂(1×10^-4mol·L^-1) had no effect on the vasodilation of baicalein on thoracic aortas induced by NE, but indomethacin (INDO,1×10^-5mol·L^-1) and glibenclamide (1×10^-5mol·L^-1) did block the vascular effect of baicalein. In the absence of extracellular Ca²⁺ pre-incubation of the aortic rings with baicalein reduced significantly the contraction induced by NE. Conclusion: BAI can lead to a significantly relaxation in rat aortic rings. The effects are dependent on the concentrations, the role of endothelium-dependent and endothelium-independent characteristics. Moreover, prostaglandin(PGI₂) pathway might be involved in the endothelium-dependent relaxation. The other mechanism was related to the inhibition of K_ATP channel, voltage-dependent Ca²⁺channel and receptors-operate Ca²⁺ channel.