葛胺酮对在体和离体动物脑动脉舒张作用的研究

Relaxation of Cerebral Arteries by Puerarin Derivative Geonone in Vitro and in Vivo

目的研究葛胺酮对在体和离体动物脑动脉的舒张作用。方法在体实验采用激光多普勒血流仪,连续动态观察葛胺酮对正常大鼠脑血流灌注压、血压(收缩压、舒张压、平均动脉压)、心率、心电图指标的的影响。体外实验采用分离犬基底动脉条,分别以重酒石酸去甲肾上腺素(5 mg·L-1),KCl(3 mol·L-1),5-羟色胺(3.3 mg·L-1)收缩效应的百分率作为评价抑制强度的指标,研究葛胺酮对基底动脉的舒张作用强度及特点。结果在体实验观察到葛胺酮25、50、100 mg·kg-1对大鼠脑血流量灌注压均有增加作用,100 mg·kg-1组比给药前脑血流增加了2～3倍。葛胺酮在增加脑血流量的同时对收缩压、舒张压均有短暂的降压作用,舒张压下降幅度大于收缩压,平均血压下降了10～40 mmHg。体外实验发现葛胺酮0.01、0.1 mg·ml-1对重酒石酸去甲肾上腺素、KCl、5-羟色胺诱导的犬基底动脉收缩均有明显的抑制作用,其舒张率达21%～99%。结论葛胺酮具有增加脑血流量同时降低血压的作用,优于葛根素。其增加脑血流量的作用与其舒张动脉的作用有关。葛胺酮可能是一个多靶点的血管紧张抑制剂,对脑缺血可能具有一定的保护作用,值得进一步研究。

Objective To study the relaxation effect of cerebral arteries by puerarin derivatives（Geonone,G20） in vitro and in vivo.Methods The effect of G20 on cerebral artery was dynamically investigated by laser Doppler flowmeter.Indicators monitored included blood flow perfusion pressure,blood pressure（systolic pressure,diastolic pressure,mean arterial pressure）,heart rate and ECG.The vasodilatation effect of G20 was evaluated on the separated dog basilar artery treated with tartaric acid re-norepinephrine（NE） 5 mg · L-1,KCl 3 mol · L-1 and 5-HT 3.3 mg · L-1 separately.Results G20 25,50,100 mg · kg-1 markedly increased perfusion pressure in rats.G20 100 mg · kg-1 increased cerebral blood flow 2-3 fold compared with sham group.Despite the increase in cerebral blood flow,the systolic pressure and diastolic blood pressure were temporarily lowered.The diastolic blood pressure decreased more significantly than systolic blood pressure.Blood pressure decreased by an average of 10-40 mmHg.In vitro experiments found that G20 0.01 and 0.1 mg · ml-1 significantly inhibited NE,KCl,and 5-HT-induced contraction of dogs basilar artery.The diastolic rate ranged from 21% to 99%.Conclusion G20 may be a multi-target inhibitor of angiotensin by increasing cerebral blood flow and reducing blood pressure.It may protect against brain ischemia.