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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。
This study aimed to investigate the effects of isoliquiritigenin (ISL) on cerebral basilar artery in spontaneously hypertensive rats (SHR). Before and after ISL intervention, the change of systolic pressure was observed by tail arterial manometer, and the cerebral basilar artery segments were isolated and prepared. The cerebral basilar artery of SHR was treated 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 cerebral basilar artery was measured by pressure-type arteriolar instrument to prepare SHR brain base The changes of the currents of large-conductance calcium-activated potassium channels (BKCa) were observed using whole-cell patch clamp recording technique. The changes of c-GMP in cerebral basilar artery of SHR were detected by ELISA . The results showed that SHR systolic blood pressure decreased from (218.3 ± 1.6) mmHg to (119.2 ± 1.9) mmHg after 14 days of ISL intervention (P <0.01, n = 6) compared with Wistar-Kyoto (P <0.01, n = 6); ISL significantly increased the outward current density of SHR basilar artery smooth muscle cells (P <0.01, n = 6) , The enhancement was blocked by 1 × 10-3 mol / L tetraethylammonium (BKCa channel blocker), while 3 × 10-4 mol / L 4-aminopyridine (Kv channel blocker) 1 × 10-5 mol / L methylene blue (soluble guanylate cyclase blocker) inhibited the outward current density of smooth muscle cells enhanced by ISL (P <0.05, n = 6). ISL significantly increased c GMP level in basilar artery of SHR (P <0.05, n = 6). The above results suggest that ISL may play a role in relaxing the basilar artery of SHR by increasing the content of cG MP in basilar artery smooth muscle cells and enhancing the outward current mediated by BKCa channel.