论文部分内容阅读
研究金丝桃苷(hyperoside,Hyp)对大鼠离体大脑中动脉(middle cerebral artery,MCA)血管内皮功能的影响,探讨其可能存在的机制。采用动脉加压灌注法测定脑血管舒缩功能和细胞膜电位记录法测定血管平滑肌细胞膜静息电位,观察Hyp(1×10-6~1×10-4mol·L-1)对U46619(1×10-7mol·L-1)预收缩大鼠MCA的作用。结果发现,累加浓度的Hyp可诱导U46619预收缩大鼠离体MCA产生明显浓度依赖性的舒张作用和血管平滑肌细胞膜静息电位超极化反应,其最大舒张率为(73.2±6.1)%,最大超极化幅度为(-13.2±2.2)m V。去除血管内皮细胞后,Hyp仍有一定的舒张反应和超极化作用,但其作用明显减弱,与血管内皮完整组比较,差异显著(P<0.01);在合用一氧化氮合酶(NOS)抑制剂L-NAME(3×10-5mol·L-1)和前列环素(PGI2)合成酶抑制剂Indo(1×10-5mol·L-1)后,Hyp仍可介导大鼠MCA产生显著的舒张反应和超极化作用;1×10-3mol·L-1Ca2+激活性钾通道(KCa)阻断剂TEA或1×10-4mol·L-1胱硫醚-γ-裂解酶(CSE)抑制剂PPG可明显减弱Hyp诱导大鼠MCA产生的非NO非PGI2样舒张作用和超极化反应;外源性硫化氢(H2S)的供体Na HS(1×10-5~1×10-3mol·L-1)或H2S合酶(CSE)底物L-Cys(1×10-5~1×10-3mol·L-1)可介导大鼠MCA产生一定的舒张作用和超极化反应。结果表明,Hyp可诱导大鼠MCA产生内皮依赖性和较弱的内皮非依赖性血管舒张作用和超极化作用,其内皮依赖性舒张作用可能与Hyp促使MCA内皮细胞生成内源性H2S增多,继而激活KCa,使KCa通道开放,引起细胞膜超极化,进而阻滞Ca2+内流,从而产生舒张血管作用有关。
To investigate the effect of hyperoside (Hyp) on vascular endothelial function in isolated rat middle cerebral artery (MCA) and its possible mechanism. The arterial pressure perfusion method was used to measure the vasomotion and cell membrane potential recording to measure the resting potential of vascular smooth muscle cells. The effects of Hyp (1 × 10-6 ~ 1 × 10-4mol·L-1) on U46619 (1 × 10 -7mol·L-1) precontracted rat MCA role. The results showed that the cumulative concentration of Hyp induced precontracted U46619 precontracted MCA produced a significant concentration-dependent relaxation and vascular smooth muscle cell membrane resting potential hyperpolarization, the maximum relaxation rate was (73.2 ± 6.1)%, the largest The hyperpolarization amplitude was (-13.2 ± 2.2) mV. After removing vascular endothelial cells, Hyp still had some diastolic and hyperpolarization effects, but its effect was obviously weakened, which was significantly different from that of the intact vascular endothelial cells (P <0.01). In the combination of nitric oxide synthase (NOS) Hyp can still mediate MCA production in rat after L-NAME (3 × 10-5mol·L-1) and PGI2 synthase inhibitor Indo (1 × 10-5mol·L-1) Significant relaxation and hyperpolarization; 1 × 10-3mol·L-1Ca2 + KCa blocker TEA or 1 × 10-4mol·L-1 cystathionine-γ-lyase (CSE ) Inhibitor PPG could significantly attenuate non-NO non-PGI2-like diastolic and hyperpolarization induced by Hyp-induced MCA in rats. NaHS (1 × 10-5 ~ 1 × 10) donor of exogenous H2S L-Cys (1 × 10-5 ~ 1 × 10-3 mol·L-1), a substrate of H2S synthase (CSE), could mediate the relaxation and hyperactivity of MCA in rats The reaction. The results showed that Hyp induces endothelium-dependent and weakened endothelium-independent vasodilatation and hyperpolarization in rat MCA. Endothelium-dependent vasodilation may be associated with Hyp-induced increase of endogenous H2S in MCA endothelial cells, And then activate KCa, KCa channels open, causing cell membrane hyperpolarization, thus blocking Ca2 influx, resulting in vasodilatation effect.