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 and dose of picroside 11 in the treatment of cerebral ischemia are ischemia 1.5 to 2.0 h and the intraperitoneal injection doses are 10 to 20 mg/kg according to the determination results of AQP-4, MMP-9 and COX-2.
出处
《中国脑血管病杂志》
CAS
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)
