3,5-二咖啡酰奎宁酸体外透血脑屏障能力及抗大鼠脑缺血再灌注损伤作用研究

Study of 3,5-di-o-caffeoyl quinic acid on penetrating the blood-brain barrier in vitro and inhibiting cerebral ischemical reperfusion injury in rats

目的:研究灯盏细辛活性成分3,5-二咖啡酰奎宁酸的体外透血脑屏障(BBB)能力及其对大鼠脑缺血再灌注损伤的影响。方法:采用体外血脑屏障模型结合HPLC技术评价3,5-二咖啡酰奎宁酸的透血脑屏障能力。预给药3天后,采用线栓法阻塞大脑中动脉(MCA)致大鼠局灶性脑缺血再灌注损伤模型,继续给药2天后,对各组大鼠进行神经功能缺失评分,并测定大鼠的脑梗死比率及其血清中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、一氧化氮合酶(NOS)含量。结果:3,5-二咖啡酰奎宁酸0.2 mg/ml对血脑屏障的透过率可达79%;与模型对照组比较,该药18.25mg/kg、9.13 mg/kg均能不同程度提高SOD、GSH-Px、NOS的活性,降低MDA活性及大鼠脑梗死比率与其神经行为学评分水平。结论:3,5-二咖啡酰奎宁酸能很好的透过血脑屏障,可通过降低大鼠脑梗死比率,增加脑缺血再灌注损伤大鼠血清SOD、GSH-Px、NOS活性,降低MDA含量,并改善其神经行为学体征,产生脑缺血保护作用。

Objective： To explore the effect of 3,5-di-o-caffeoyl quinic acid on ischemical reperfusion injury in rats and the ability crossirs blood- brain barrier（BBB） in vitro. Methods： Blood brain barrier model was established and the active component was detected by HPLC. The model of middle cerebral artery occlusion（MCAO） was built by suture embolism in rats after rats were administered for 3 days. The rats were administered for two more days, then the nerve function score was recorded cerebral infarction proportion, SOD, MDA, GSH-Px and NOS in ratsblood serum were detected. Results： Compared with control group, the ability to penetrate BBB of 3,5-di-O-eaffeoyl quinie acid （0.2 mg/ ml） is much higher than that of erigeron injection. Compared with model group,3,5-di-O-caffeoyl quinic acid（ 18.25,9.13 mg/kg）can de- crease cerebral infarction ratio and score, enhance the activities of SOD, GSH-Px, NOS, and decrease the content Of MDA in rats （ P 〈 0.05,0. 01 ）. Conclusion： These findings indicate that 3,5-di-O-caffeoyl quinic acid could cross BBB well, and decrease cerebral infarction propor- tion;enhance the activities of SOD, GSH-Px, NOS;decrease the content of MDA and improve neurologic injury in rats. There fore 3, 5-di-o-caffeoyl quinic acid could relieve the damages caused by ischemical reperfusion injury.