天麻素对大鼠离体胸主动脉血管环的作用及机制研究

Effect and mechanism of gastrodin on isolated thoracic aorta rings in rats

目的观察天麻素对大鼠离体胸主动脉环的作用,并探讨其作用机制。方法采用离体动脉环灌流方法,观察累加浓度天麻素对大鼠离体胸主动脉环的直接作用;同法观察不同浓度天麻素(5μmol/L、50μmol/L、100μmol/L、150μmol/L、200μmol/L、250μmol/L)对10-6mol/L去氧肾上腺素(PE)预收缩有内皮和去内皮血管环的作用;用无Ca2+K-H液和不同浓度天麻素孵育对PE收缩去内皮血管环的作用;观察200μmol/L天麻素对60 mmol/L KCl预收缩血管环的作用。结果天麻素直接作用于血管环时,天麻素组与对照组血管紧张度比较差异无统计学意义(P>0.05);天麻素(≥50μmol/L)作用于PE预收缩血管环时,有内皮天麻素组血管环舒张率分别高于有内皮对照组[(41.9±8.9)%、(57.6±9.1)%、(65.0±10.2)%、(75.6±11.7)%、(81.9±12.0)%vs(10.5±1.6)%、(19.4±5.9)%、(22.6±7.2)%、(24.9±6.8)%、(25.1±7.3)%、P<0.05],去内皮天麻素组血管环舒张率分别高于去内皮对照组[(20.6±2.9)%、(36.5±8.2)%、(43.7±9.3)%、(55.7±9.6)%、(58.7±9.6)%vs(9.8±2.1)%、(15.8±4.7)%、(18.6±6.5)%、(20.3±5.0)%、(21.5±5.1)%,P<0.05],且均有浓度依赖性,多组间比较F值分别为5.67,5.99,6.11,6.47,7.05,P<0.05;天麻素作用于无钙K-H液中PE收缩去内皮血管环时,实验组舒张率[(5.1±1.2)%]小于对照组[(12.8±3.7)%],差异有统计学意义(t=5.599,P<0.05)。天麻素处理作用于60 mmol/L KCl预收缩的血管环时,天麻素组[(96.7±8.6)%]与对照组[(98.6±7.9)%]张力变化差异无统计学意义(t=0.581,P>0.05)。结论天麻素对正常血管无舒张作用;天麻素能舒张PE预收缩的血管,其机制是通过抑制血管平滑肌IP3受体介导的内钙释放;它不能抑制α1受体依赖性钙通道和电压依赖性钙通道;天麻素舒张PE收缩的血管的作用有内皮依赖性和浓度剂量依赖效应。

Objective To observe the effect and mechanism of gastrodin on isolated thoracic aorta rings in rats.Methods A perfusion model of isolated thoracic aorta ring in rats was applied to observe the direct effect of cumulative gastrodin on isolated thoracic aorta rings in rats. The same method was also used to explore the effects of the different concentration gastrodin(5 μmol/L, 50 μmol/L, 100 μmol/L, 150 μmol/L, 200 μmol/L, 250 μmol/L) on endothelium-intact/denuded aorta rings pre-contracted with 10-6mol/L phenylephrine(PE). PE was used to contract the aorta rings incubated by 200 mmol/L gastrodin in the Ca2 +free K-H solution, and the effect of 200 mmol/L gastrodin on aorta rings pre-contracted with 60 mmol/L KCl was observed. Results With the direct effect of gastrodin on the endothelium-intact vascular ring, there was no significant difference between the gastrodin group and the control group(P>0.05) on the vascular tension. With the effect of cumulative concentration of gastrodin(≥50 μ mol/L) on PE pre-contracted vascular ring were studied, the vascular ring relaxation rate in endothelium-intact gastrodin group and endothelium-denuded gastrodin group were significantly higher than control group [(41.9 ± 8.9)%,(57.6 ± 9.1)%,(65.0 ± 10.2)%,(75.6 ± 11.7)%,(81.9±12.0)% vs(10.5±1.6)%,(19.4±5.9)%,(22.6±7.2)%,(24.9±6.8)%,(25.1±7.3)%, P<0.05]; Moreover, the rate of relaxation of vascular rings in the endothelium-intact gastrodin group were higher than in the endothelium-denuded gastrodin group [(20.6 ± 2.9)%,(36.5 ± 8.2)%,(43.7 ± 9.3)%,(55.7 ± 9.6)%,(58.7 ± 9.6)%) vs(9.8 ± 2.1)%,(15.8 ± 4.7)%,(18.6 ± 6.5)%,(20.3 ± 5.0)%,(21.5 ± 5.1)%, P<0.05]. F values of multi-group were respectively 5.67, 5.99, 6.11, 6.47,7.05(P<0.05). When the experiment was performed on the effect gastrodin on PE pre-contracted vascular ring in the calcium free fluid K-H solution, the relaxation rate in gastrodin group [(5.1 ± 1.2)% ] was lower in the control group[(12.8 ± 3.7)% ](P<0.05); When the effect of gastrodin on 60 mmol/L KCl pre-contracted thoracic aortic rings, there was no significant difference between the gastrodin group [(96.7±8.6)%] and the control group [(98.6±7.9)%] in the vascular tension(P>0.05). Conclusion Gastrodin has no effect on intact aorta ring. The relaxation mechanism of Gastrodin on aorta rings pre-contracted with PE is through the inhibition of release of Ca2 +from the endoplasmic reticulum.Gastrodin can not inhibit the receptor-operated Ca2+channel and the voltage-dependent Ca2+channel. Therefore, the relaxation effect of gastrodin is endothelium-dependent and concentration-dependent.