胡黄连苷Ⅱ对大鼠脑缺血损伤的抗氧化作用及剂量优化研究

Study of Picroside Ⅱ on Antioxidation and Dose Optimization in the Rats of Cerebral Ischemic Injury

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(BCCAO)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,应用黄嘌呤氧化酶法、化学比色法和光化学法分别检测血清和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。结果胡黄连苷Ⅱ治疗脑缺血损伤的最佳效果:根据血清SOD、GSHPx和CAT活性分析,分别为脑缺血1.5 h腹腔注射20 mg.kg-1、1.5 h/10 mg.kg-1和1.5 h/20 mg.kg-1体重。根据脑组织SOD、GSHPx和CAT活性分析,分别为脑缺血1.5 h腹腔注射20 mg.kg-1、2.0 h/20 mg.kg-1和1.5 h/10 mg.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治疗脑缺血损伤的最佳治疗时间窗和剂量为脑缺血1.5～20 h腹腔注射10～20 mg.kg-1体重。

Objective To optimize the best dose and time window of picroside lI in the treatment of cerebral ischemic injury in the rats through orthogonal test. Methods BCCAO method was adopted to set up forebrain isehemia in rats. The orthogonal test was used to design the group division. The intervention of picro- side II was given via intraperitoneal injection. Xanthinoxidase, chemical colorimetry and photochemical meth- od were used to detect the activity of SOD, GSHPx and CAT in serum and brain tissue. Results Picroside II received the best effect on cerebral ischemic injury. According to the analysis on the serum activity of SOD, GSHPx and CAT,picroside II was injected intraperitoneaUy at 20 mg ·kg^-1and 10 mg ·kg^-1 of body weight in 1.5 h cerebral ischemia, and 20 mg·kg^-1 in 2.0 h cerebral ischemia separately. According to the analysis on the activity of SOD, GSHPx and CAT in brain tissue, picroside II was injected intraperitoneally at 20 mg·kg^-1 in 1.5 h cerebral ischemia,20 mg ·kg^-1in 2.0 h cerebral ischemia and 10 mg ·kg^-1 of body weight in 1.5 h cerebral ischemia separately. Conclusion The optimal time window and dose of picroside II in the treatment of cerebral ischemic injury is 10 -20 mg ·kg^-1 of body weighty in intraperiotoneal injection in 1.5 - 2.0 h of cerebral ischemia.