胡黄连苷Ⅱ对脑缺血损伤大鼠抗氧化作用的时间窗及剂量选择

Selection of Dose and Time of Picroside Ⅱ According to Antioxidant Effect on Rats with Cerebral Ischemic Injury

目的:通过正交试验优化胡黄连苷Ⅱ在大鼠脑缺血损伤中抗氧化作用的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,硫代巴比妥酸法、硝酸还原酶法和光化学法分别测定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,黄嘌呤氧化酶法、化学比色法和光化学法分别检测脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)和过氧化氢酶(CAT)的活性。根据用药剂量最小化和治疗时间窗最大化原则综合评价。结果:胡黄连苷Ⅱ治疗脑缺血损伤的最佳效果:根据脑组织MDA、NO和H2O2含量分析,分别为脑缺血1.5小时腹腔注射10mg·kg-1、20mg·kg-1和2小时腹腔注射20mg·kg-1;根据脑组织SOD、GSHPx和CAT活性分析,分别为脑缺血1.5小时腹腔注射20mg·kg-1、2小时腹腔注射20mg·kg-1和1.5小时腹腔注射10mg·kg-1。结论: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1.5～2.0小时腹腔注射10～20mg·kg-1。

Objective：To optimize the therapeutic dosage and time according to antioxidant effect of picrosede Ⅱ on rats with cerebral ischemic injury by orthogonal test. Methods： The forebrain ischemia models were estab- lished by bilateral common carotid artery occlusion （BCCAO） methods. The successful models were divided ac- cording to orthogonal experimental design and conduct intervention treatment by injecting picrosideⅡ intraper- itonenally. The concentrations of malondialdehyde （ MDA）, nitric oxide （NO） and hydrogenperoxide （ H2O2 ） in brain tissue were respectively determined by thiobarbituric acid assay, nitratase reduase assay and chemilumi- nescence immunoassay. The activities of superoxide dismutase （ SOD）, glutathione peroxidase （GSHPx） and catalase （CAT） in brain tissue were respectively determined by xanthinoxidase assay, chemical colorimetry and chemiluminescence immunoassay. Results： The best therapeutic effects of picroside Ⅱ on cerebral iscbemic inju- ry were isehemia 1.5h with 10mg .kg-1 , 20mg . kg-1 and 2. Oh with 20mg . kg-1 according to the concentra- tions of MDA, NO and H2O2 in brain tissue; ischemia 1.5h with 20mg . kg-1, 2. Oh with 20mg . kg-1 and 1.5h with 10mg. kg-1 according to the activities of SOD, GSHPx and CAT in brain tissue. Conclusions： The optimized therapeutic dose and time is injecting picroside Ⅱ peritonenally with 10 -20mg. kg- 1 at ischemia 1.5 - 2. Oh in cerebral ischemic injury.