胡黄连苷Ⅱ治疗脑缺血的机制及最佳剂量和时间窗研究

Research on the Mechanism,Optimal Dose and Time Window of Picroside Ⅱ in the Treatment of Cerebral Ischemia

目的通过正交试验优化胡黄连苷Ⅱ治疗大鼠脑缺血损伤的最佳剂量和时间窗。方法应用双侧颈总动脉结扎法建立大鼠前脑缺血模型，按正交试验设计分组，经腹腔注射胡黄连苷Ⅱ干预治疗，酶联免疫吸附法检测血清水通道蛋白4（AQP4）、基质金属蛋白酶9（MMP9）、环氧合酶2（COX2）的含量，综合评价胡黄连苷Ⅱ治疗脑缺血损伤的疗效。结果胡黄连苷Ⅱ治疗脑缺血损伤的最佳效果。根据血清AQP4含量分析为脑缺血2．0h腹腔注射20mg·kg^-1体重；根据血清MMP9含量分析为脑缺血1．5h／20mg·kg^-1体重．根据血清COX2含量分析为脑缺血1．5h／10mg·kg^-1体重。结论从用药剂量最小化和治疗时间窗最大化原则综合评价．胡黄连苷Ⅱ治疗脑缺血损伤的治疗时间窗和剂量为脑缺血1．5～2．0h腹腔注射10-20mg／kg体重。

Objective To optimize the therapeutic dose and time window of picrosede II by orthogonal test in cerebral ischemic injury in rats. Methods The forebrain ischemia models were established by bilateral common carotid artery occlusion （BCCAO） methods. The successful models were randomly divided into sixteen groups according to orthogonal experimental design and intervented by injecting picroside Ⅱ intraperitoneally at different ischemic time with different dose. The concentrations of aquaporins 4 （AQP4）, matrix metalloproteinases 9 （MMP9） and cyclooxygenase 2 （COX2） in serum were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside Ⅱ on cerebral ischemic injury. Results The best therapeutic time window and dose of picroside Ⅱ in cerebral ischemic injury were as followed： ①ischemia 2.0 h with 20 mg ·kg^-1 body weight according to the concentration of AQP4; ② ischemia 1.5 h with 20 mg·kg^-1 according to the concentrations of MMP9; ③ischemia 1.5 h with 10 mg·kg^-1 according to the concentrations of COX2 in serum. Conclusions From the principle of lowest therapeutic dose with longest time window, the optimized therapeutic dose and time window is injecting picroside Ⅱ intraperitoneally with 10 - 20 mg·kg^-1 body weight at ischemia 1.5 - 2.0 h in cerebral ischemic injury.