胡黄连苷Ⅱ在大鼠脑缺血损伤中治疗剂量和时间窗的优化  

Optimizing of therapeutic dose and time window for picroside Ⅱ in cerebral ischemic injury in rats

作　　者：赵丽[1] 李晓丹[1] 郭云良[1] 逄芳芳[1] 常翠翠[1] 

机构地区：[1]青岛大学医学院中西医结合中心,266021

出　　处：《中国脑血管病杂志》2013年第7期373-378,共6页Chinese Journal of Cerebrovascular Diseases

基　　金：国家自然科学基金资助项目(81041092;81274116)

摘　　要：目的探讨胡黄连苷Ⅱ治疗大鼠脑缺血损伤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脑缺血模型,将48只大鼠模型,按二因素四水平[L16(45)]正交试验设计分组。治疗时间窗设定缺血1.0、1.5、2.0、2.5 h,共4个水平,治疗剂量设定5、10、20、40 mg/kg共4个水平。按照设定剂量经腹腔注射胡黄连苷Ⅱ干预治疗,采用酶联免疫吸附法(ELISA)检测血清和脑组织水通道蛋白4(AQP-4)、基质金属蛋白酶9(MMP-9)和环氧合酶2(COX-2)的水平,评价胡黄连苷Ⅱ治疗大鼠脑缺血损伤的疗效。结果①根据血清和脑组织AQP-4水平分析结果,胡黄连苷Ⅱ治疗脑缺血损伤的最佳治疗时间窗和剂量分别为脑缺血2.0 h,腹腔注射20 mg/kg;脑缺血1.5 h,腹腔注射20 mg/kg。②根据血清和脑组织MMP-9水平分析结果,最佳治疗时间窗和剂量分别为脑缺血1.5 h,腹腔注射20 mg/kg;脑缺血2.0 h,腹腔注射20 mg/kg。③根据血清和脑组织COX-2水平分析结果,最佳治疗时间窗和剂量分别为脑缺血1.5 h,腹腔注射10 mg/kg;脑缺血1.5 h,腹腔注射20 mg/kg。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,根据AQP-4、MMP-9、COX-2测定结果,胡黄连苷Ⅱ治疗脑缺血损伤的最佳治疗时间窗和剂量为脑缺血1.5～2.0 h,腹腔注射剂量10～20 mg/kg。Objective To optimize the therapeutic dose and time window of picrosede Ⅱ by orthogo-nal test in cerebral ischemie injury in rats. Methods A rat cerebral ischemia model was induced by u-sing bilateral carotid artery ligation method. A total of 48 animals were grouped according to an orthogonal design with 2 factors and 4 levels （ [ L16 （4^5 ] ）. The therapeutic time widows were set for four levels ： cere-bral ischemia 1.0, 1.5, 2.0 and 2.5 h, and the therapeutic drug doses were set for four levels ： 5, 10, 20 and 40 mg/kg body weight. In accordance with the setting doses, the rats were intervened by intraperitone- ally injecting picroside Ⅱ. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of aquaporins 4 （AQP-4） , matrix metalloproteinases 9 （MMP-9） and cyclooxygenase 2 （ COX-2 ） in serum and brain tissue. The efficacy of picroside Ⅱ in the treatment of cerebral ischemic injury was evaluated comprehensively. Results ①The optimal therapeutic time window and dose of pieroside Ⅱ in the treat- ment of cerebral ischemic injury were ischemia 2.0 h and intraperitoneal injection of 20 mg/kg, and cere-bral ischemia 1.5 h and intraperitoneal injection of 20 mg/kg according to the levels of AQP-4 in serum and brain tissue. ②The optimal therapeutic time window and dose of pieroside Ⅱ in the treatment of cerebral ischemie injury were ischemia 1.5 h and intraperitoneal injection of 20 mg/kg, cerebral ischemia 2.0 h and intraperitoneal injection of 20 mg/kg according to the analysis results of MMP-9 levels in serum and brain tissue. ③ The optimal therapeutic time window and dose were cerebral ischemia 1.5 h and intraperitoneal injection of 10 mg/kg, and cerebral ischemia 1.5 h and intraperitoneal injection of 20 mg/kg according to the analysis results of COX-2 levels in serum and brain tissue. Conclusion According to the principles of the dose minimization and the treatment time window maximization, they evaluated comprehensively. The optimal therapeutic window a

关 键 词：脑缺血 水通道蛋白4 基质金属蛋白酶9 胡黄连苷Ⅱ 治疗剂量 时间窗 大鼠 

分 类 号：R277.7[医药卫生—中医学]