本文旨在研究异甘草素(isoliquiritigenin,ISL)对自发性高血压大鼠(spontaneously hypertensive rat,SHR)脑基底动脉的影响。在给予ISL干预前后,用尾动脉测压仪观察收缩压的变化,分离和制备脑基底动脉血管段,对SHR脑基底动脉依次给予1×10^-5 mol/L苯肾上腺素(phenylephrine,PE)、1×10^-5 mol/L PE+1×10^-4 mol/L ISL和1×10^-5 mol/L PE灌流后,用压力型小动脉仪测量脑基底动脉的直径,制备SHR脑基底动脉单个血管平滑肌细胞,用全细胞膜片钳记录技术观察大电导钙激活钾通道(large-conductance calcium-activated potassium channels,BKCa)电流的变化,并用ELISA技术检测SHR脑基底动脉内c GMP水平的变化。结果表明:给予ISL干预14天后,SHR收缩压由(218.3±1.6)mmH g降低至(119.2±1.9)mmH g(P〈0.01,n=6),与Wistar-Kyoto(WKY)大鼠相比没有显著差异;1×10^-4 mol/L ISL舒张SHR脑基底动脉(P〈0.01,n=6);ISL可显著增加SHR脑基底动脉平滑肌细胞外向电流密度(P〈0.01,n=6),该增强作用可被1×10^-3 mol/L四乙胺(BKCa通道阻断剂)所阻断,而3×10^-4 mol/L 4-氨基吡啶(Kv通道阻断剂)对ISL增强的平滑肌细胞外向电流密度无明显影响;1×10^-5 mol/L亚甲蓝(可溶性鸟苷酸环化酶阻断剂)可以抑制ISL增强的平滑肌细胞外向电流密度(P〈0.05,n=6);ISL可明显增加SHR脑基底动脉内c GMP水平(P〈0.05,n=6)。以上结果提示:ISL可能通过增加脑基底动脉平滑肌细胞cG MP含量,增强BKCa通道介导的外向电流,从而发挥舒张SHR脑基底动脉的作用。
The purpose of the present study is to investigate the effect of isoliquiritigenin(ISL) on the cerebral basilar artery in spontaneously hypertensive rats(SHR). The change of SHR systolic pressure was measured by tail artery pressure measurement instrument before and after ISL intervention. After perfusion with 1 × 10^-5 mol/L phenylephrine(PE), 1 × 10^-5 mol/L PE + 1 × 10^-4 mol/L ISL and 1 × 10^-5 mol/L PE, the diameter of the cerebral basilar artery separated from SHR was measured by pressure myograph. The current of large-conductance calcium-activated potassium(BKCa) channel of SHR single vascular smooth muscle cell(VSMC) was recorded by whole-cell patch-clamp technique and the cGMP levels of basilar artery was evaluated by ELISA. The results showed that 1) after intervention with ISL for 14 days, the systolic pressure of SHR was decreased from(218.3 ± 1.6) mm Hg to(119.2 ± 1.9) mm Hg(P 0.01), but there was no difference in systolic pressure between ISL-treated SHR and Wistar-Kyoto(WKY) rat; 2) 1 × 10^-4 mol/L ISL relaxed the SHR cerebral basilar artery(P 0.01); 3) ISL significantly increased the outward current density of VSMC from SHR cerebral basilar artery(P 0.01, n = 6), and the effect could be reversed by 1 × 10^-3 mol/L TEA(a BKCa channel inhibitor), but 3 × 10^-4 mol/L 4-AP(a Kv channel inhibitor) had no effect on the enhanced current density induced by ISL in VSMC; 4) 1 × 10^-5 mol/L Methylene blue(a sGC inhibitor) significantly inhibited the ISL-enhanced current density in VSMC(P 0.05, n = 6); 5) ISL significantly increased the cGMP level of SHR basilar artery(P 0.05, n = 6). The results suggest that the role of the ISL in relaxing the SHR cerebral basilar artery may be related to its effect in enhancing BKCa current by increasing the levels of c GMP in the VSMC.