胡黄连苷Ⅱ对大鼠脑缺血损伤后髓鞘碱性蛋白表达的影响  

Effect of picroside Ⅱ on expression of myelin basic protein after cerebral ischemia injury in rats

作　　者：赵丽[1] 郭云良[1] 

机构地区：[1]青岛大学附属医院脑血管病研究所,山东青岛266003

出　　处：《中国病理生理杂志》2014年第4期584-591,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81041092;No.81274116)

摘　　要：目的：用正交试验法验证胡黄连苷Ⅱ对大鼠脑缺血损伤的神经保护作用并优化其最佳治疗剂量及时间窗。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。固绿髓鞘染色法观察神经纤维髓鞘变化；免疫组织化学法和Westernblotting定性、定量检测髓鞘碱性蛋白（MBP）的表达；RT．PCR检测MBPmRNA水平。结果：胡黄连苷Ⅱ可上调大鼠脑缺血损伤后MBP表达，减少脱髓鞘；其最佳治疗时间和剂量，根据固绿髓鞘染色显示为脑缺血2．0h腹腔注射胡黄连苷Ⅱ10mg／kg；免疫组织化学法分析为脑缺血2．0h腹腔注射10ms／kg；Westernblotting分析为脑缺血2．0h给予10ms／kg；RT-PCR显示为脑缺血1．5h给予20ms／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，胡黄连苷Ⅱ对大鼠脑缺血损伤的最佳治疗时间窗为脑缺血1．5～2．0h，最佳治疗剂量为腹腔注射10～20ms／kg。AIM： To verify the neuroprotective effect and optimize the therapeutic dose and time window of picroside II on cerebral ischemic injury in rats. METHODS ： The forebrain ischemia model was established by the method of bilateral common carotid artery occlusion （BCCAO）. The successful model rats were randomly divided into 16 groups according to orthogonal design and treated by intraperitoneal injection of picroside lI at different ischemic time poinis and different doses. The changes of the nerve fiber myelin were observed by fast green staining. The immunohistochemical assay and Western blotting were used to quantitatively and qualitatively determine the expression of myelin basic protein （MBP）. The mRNA level of MBP in the brain tissues was tested by reverse transcription polymerase chain reaction （RT-PCR）. RE- STILTS： Picroside II increased the expression of MBP and decreased demyelination after cerebral ischemic injury. The best therapeutic time window and dose were： （ 1 ） ischemia for 2.0 h with picroside I1 at dose of 10 mg/kg according to the results of fast green staining; （2） ischemia for 2.0 h with the dose of 10 mg/kg according to the results of immunohisto- chemical assay; （3） ischemia for 2.0 h with the dose of 10 mg/kg according to the analysis of Western blotting; （4） is- chemia for 1.5 h with the dose of 20 mg/kg according to the detection of RT-PCR. CONCLUSION： Given the principle of the lowest therapeutic dose with the longest time window, the optimized therapeutic dose and time window for rat cerebral ischemic injury is intraperitoneal injection of picroside I1 at the doses of 10 ~ 20 mg/kg and the time window of ischemia for 1.5 -2.0 h.

关 键 词：胡黄连苷II 脑缺血 大鼠 髓鞘碱性蛋白 

分 类 号：R363[医药卫生—病理学]