黄芩苷脂质体对脑缺血再灌注损伤大鼠药效学考察及PK-PD模型的建立

Pharmacodynamic study and PK-PD model of baicalin liposome on cerebral ischemia-reperfusion injury in rats

目的考察静脉注射黄芩苷脂质体(baicalin liposome, BA-LP)后,对脑缺血再灌注损伤模型大鼠(cerebral ischemia reperfusion, I/R)的疗效及经时变化和抗氧化作用的药动学-药效学(PK-PD)相关性。方法采用线栓法制备大鼠中动脉栓塞模型(MCAO),静脉注射BA-LP后从神经行为学特征、脑梗死率和脑含水量的变化情况考察其治疗效果,测定给药后血清中SOD和LDH活性经时变化曲线,并结合药动学数据,利用DAS3.1.1构建药-效相关性模型。结果造模后大鼠神经功能受损,含水量明显增高(P<0.05),脑梗死面积明显增加(P<0.05),血浆和脑中SOD和LDH水平有明显变化。静脉注射BA-LP干预后,其SOD水平升高,LDH活性降低,明显改善其神经功能状态,且SOD和LDH活性的变化与BA药效的发挥具有一定的滞后性。结论 BA-LP对I/R有明显的神经保护作用,其可能是通过升高SOD水平,降低LDH活性达到抗氧化的作用。

Objective To investigate the effect of baicalin liposome on cerebral ischemia-reperfusion injury in rats, and the relationship between the pharmacokinetic-pharmacodynamic(PK-PD) changes. Methods MCAO model was established by thread embolization in rats. The therapeutic effect was evaluated by neurobehavioral characteristics, cerebral infarction rate and brain water content changes after intravenous injection of BA-LP. The time-varying curves of SOD and LDH activities in serum were measured after administration. A PK-PD model was established by DAS3.1.1.Results The results showed that after MCAO surgery, the neurological function, the water content increased significantly(P< 0.05), the area of cerebral infarction increased significantly(P< 0.05), and the levels of SOD and LDH in plasma and brain significantly improved. After the intervention of BA-LP via intravenous administration, the level of SOD increased and the activity of LDH decreased, which significantly improved the neurological function. Moreover, the changes of SOD and LDH activities lag behind the BA. Conclusion BA-LP has obvious neuroprotective effect on I/R, which may be related to its function of anti-oxidant by increasing SOD level and decreasing LDH activity.