胡黄连苷Ⅱ在大鼠脑缺血损伤中的抗氧化作用及其最佳治疗剂量和时间窗

摘要

Objective To optimize the therapeutic dose and time window of picroside Ⅱ in treating cerebral ischemic injury in rats by orthogonal test. Methods The forebrain ischemia models were established by bilateral common carotid artery occlusion (BCCAO) method. The successful models were randomly grouped according to orthogonal experimental design and treated by injecting picroside Ⅱintraperitoneally at different ischemic time with different doses. The concentrations of MDA, NO and H2O2 in serum and brain tissue were respectively determined by thiobarbituric acid assay, nitratase reductase assay and chemiluminescence immunoassay. Results The optimized composition of the therapeutic dose and time window of picroside Ⅱ in cerebral ischemic injury were ischemia 1.5 h with 10 mg/kg, 1.5 h with 20 mg/kg and 1.5 h with 10 mg/kg body weight according to the expressions of MDA, NO and H2O2 in serum, and ischemia 1.5 h with 10 mg/kg, 1.5 h with 20 mg/kg and 1.5 h with 20 mg/kg body weight according to the expressions of MDA, NO and H2O2 in brain tissue. Conclusion On the basis of the principle of lowest therapeutic dose with longest time window, the optimized composition of the therapeutic dose and time window in cerebral ischemic injury is injecting picroside Ⅱ intraperitoneally with 10-20 mg/kg body weight at ischemia 1.5 h.%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，按照正交试验设计分组，经腹腔注射胡黄连苷Ⅱ干预治疗。应用硫代巴比妥酸法、硝酸还原酶法和光化学法，分别测定血清和脑组织中脂质过氧化物丙二醛(MDA)、一氧化氮(NO)和过氧化氢(H2O2)的含量。结果胡黄连苷Ⅱ治疗脑缺血损伤的最佳效果，根据血清MDA、NO和H2O2含量分析，分别为脑缺血1.5 h腹腔注射10、20、10 mg/kg体质量。根据脑组织MDA、NO和H2O2含量分析，分别为脑缺血1.5 h腹腔注射10、20、20 mg/kg体质量。结论从用药剂量最小化和治疗时间窗最大化的角度综合评价，胡黄连苷Ⅱ治疗脑缺血损伤的治疗时间窗和剂量最佳组合为脑缺血1.5 h腹腔注射10～20 mg/kg体质量。