胡黄连苷Ⅱ对脑缺血损伤后血清自由基水平和抗氧化酶活性的影响

Influence of PicrosideⅡon Serum Level of Free Radical and Activity of Anti-Oxidase in Cerebral Ischemic Injury in Rats

目的：通过正交试验优化胡黄连苷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。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,并通过硫代巴比妥酸法、硝酸还原酶法和光化学方法分别测定血清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。黄嘌呤氧化酶法、化学比色法和光化学方法分别检测血清中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSHPx）和过氧化氢酶（CAT）的活性。结果：胡黄连苷Ⅱ治疗脑缺血损伤的最佳治疗时间窗和剂量,根据血清中MDA、NO和H2O2的含量分析,分别为1.5 h/10 mg、1.5 h/20 mg和1.5 h/10mg;根据血清中SOD、GSHPx和CAT的活性分析,分别为1.5 h/20 mg、1.5 h/10 mg和1.5 h/20 mg。结论：根据用药剂量最小化和治疗时间窗最大化的原则综合评价,胡黄连苷Ⅱ治疗脑缺血损伤的最佳治疗时间窗和剂量为脑缺血1.5 h腹腔注射10～20 mg/kg体重。

Objective：To optimize the anti-oxide effect and therapeutic dose and time window of picroside 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 treated by injecting picroside Ⅱ intraperitonenally at different ischemic time points with different doses.The concentrations of malondialdehyde（MDA）,nitric oxide（NO） and hydrogenperoxide（H2O2） in serum were determined by thiobarbituric acid assay,nitratase reduase assay and chemiluminescence immunoassay respectively.The activities of superoxide dismutase（SOD）,glutathione peroxidase（GSHPx） and catalase（CAT） in serum were determined by xanthinoxidase method,chemical colorimetry and chemiluminescence immunoassay respectively.Results：The best therapeutic time window and dose of picroside Ⅱ in cerebral ischemic injury were（1） 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 concentrations of MDA,NO and H2O2 in serum;（2） ischemia 1.5 h with 20 mg/kg,1.5 h with 10 mg/kg and 1.5 h with 20 mg/kg body weight according to the activities of SOD,GSHPx and CAT in serum.Conclusion：From the principle of lowest therapeutic dose with longest time window,the optimized therapeutic dose and time window is injecting picroside Ⅱ intraperitonenally with 10-20 mg/kg body weight at ischemia 1.5 h in cerebral ischemic injury.