莫诺苷大鼠脑靶向分布研究

Study on Targeting Ddistribution of Morroniside in Rat Brain

目的:研究莫诺苷透过局造型脑缺血再灌注大鼠血脑屏障的能力。方法:建立大鼠在体脑血分布模型,探讨神经保护剂莫诺苷在正常组大鼠、假手术组大鼠和局灶性脑缺血再灌注模型组大鼠的脑靶向分布。采用线栓法制作局灶性脑缺血再灌注大鼠模型。造模成功后,3组大鼠尾静脉滴注莫诺苷溶液,待血药浓度达到稳态(55 min)后,取血和左右脑组织,采用已经建立的生物基质中莫诺苷浓度测定的LC-MS/MS方法测定大鼠血浆与脑组织中的莫诺苷浓度,并计算血脑分配系数(lg BB)。结果:莫诺苷在局造型脑缺血大鼠左右脑的lg BB分别为(1.36±0.44)和(2.26±0.13),但正常组大鼠和假手术组大鼠的lg BB值较低,药物透过该两组大鼠血脑屏障的能力较差,局造性脑缺血再灌注模型组大鼠的lg BB值明显高于正常组大鼠和假手术组大鼠。结论:较正常组大鼠和假手术组大鼠,莫诺苷可以明显透过局灶性脑缺血再灌注模型大鼠的血脑屏障。

Objective： The aim of this study was to investigate the steady-state brain-plasma concentration ratio of morroniside in focal cerebral ischemia-reperfusion model rats. Method： The in vivo rat model was established. The middle cerebral artery occlusion was induced by the intraluminal filament technique. The concentrations of morroniside in the plasma and brain of rats were determined from normal control group,shamoperated group and focal cerebral ischemia- reperfusion model group,and the blood brain partitioning（lg BB） of morroniside was calculated while the plasma concentration of morroniside was in the steady-state via intravenous drip（55 min） by LC-MS/MS. Result： Morroniside almost could not pass through the blood brain barrier in normal rats. The lg BB of morroniside in the left and right brain of focal cerebral ischemia-reperfusion model rats were（1. 36 ± 0. 44） and（2. 26 ± 0. 13）,respectively,which were significantly higher than the normal control group and sham-operated group rats. Conclusion： The results demonstrated that morroniside could pass through the blood brain barrier in rats in focal cerebral ischemia-reperfusion model group more easily than normal control and sham-operated group.