胡黄连苷Ⅱ治疗脑缺血/再灌注损伤剂量和时间窗的初步探讨

Primary study on the therapeutic dose and time window of picrosideⅡ in cerebral ischemic injury in rats

目的通过正交试验优化胡黄连苷Ⅱ治疗大鼠脑缺血/再灌注损伤的最佳剂量和时间窗。方法应用线栓法建立大鼠大脑中动脉闭塞(MCAO)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,Bedersons评分评价动物神经行为功能,氯化三苯基四氮唑(TTC)染色观察脑梗死体积,免疫组织化学检测神经元特异性烯醇化酶(NSE)和神经胶质细胞标志蛋白(S-100)表达。结果胡黄连苷Ⅱ治疗脑缺血/再灌注损伤的最佳效果,根据Bederson’s评分分析为脑缺血1.5 h给予20 mg.kg-1;根据脑梗死体积分析为脑缺血1.5 h给予20 mg.kg-1;根据NSE表达分析为脑缺血1.0 h给予20 mg.kg-1;根据S-100表达分析为脑缺血1.5 h给予20 mg.kg-1。结论从用药剂量最小化和治疗时间窗最大化的角度综合评价,胡黄连苷Ⅱ治疗脑缺血/再灌注损伤的治疗时间窗和剂量最佳组合为,脑缺血1.5 h腹腔注射20 mg.kg-1。

Aim To optimize the group of the therapeutic dose and time window of picroside Ⅱ in cerebral ischemic injury in rats by orthogonal test.Method The middle cerebral artery occlusion（MCAO） models were established by intraluminal thread methods.The successful rat models were randomly divided into sixteen groups according to orthogonal table and intervened with picroside Ⅱ at different dose and different time.The neurological behavoiral function was evaluated by Bedersons test and the cerebral infarction volume was measured by tetrazolium chloride（TTC） staining.The expressions of neuron-specific enolase（NSE） and protein and neuroglial markers protein S-100 were determined by immunohistochemisty assay.Result The optimized composition of the therapeutic dose and time window of picroside Ⅱ in cerebral ischemic injury were ischemia 1.5 h with 20 mg·kg-1 body weight according to Bedersons test,1.0 h with 20 mg·kg-1 body weight according to cerebral infarction volume,1.5 h with 20 mg·kg-1 body weight according to the expressions of NSE and S-100.Conclusion In terms of evaluation from the principle of lowest therapeutic dose with longest time window,the optimized composition of the therapeutic dose and time window of picroside Ⅱ in cerebral ischemic injury is injected peritoneally with 20 mg·kg-1 body weight at cerebral ischemic 1.5 h.