胡黄连苷Ⅱ对脑缺血损伤后细胞外信号调节蛋白激酶通路的影响及神经保护作用  

The effect of picroside Ⅱ on the ERK1/2 signal transduction pathway and its neuroprotective effect on the cerebral ischemic injury in rats

作　　者：王婷婷[1] 翟丽[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,青岛266003

出　　处：《中华行为医学与脑科学杂志》2016年第2期97-102,共6页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目(81041092，81274116)@@@@ National Natural Science Foundation of China

摘　　要：目的探讨胡黄连苷Ⅱ对脑缺血损伤后细胞外信号调节蛋白激酶1／2（ERKl／2）信号转导通路的影响及其神经保护作用机制。方法成年健康雄性Wistar大鼠100只，应用线栓法建立大鼠脑缺血（MCAO）模型，随机分为对照组、模型组、治疗组、LPS组和U0126组。改良神经功能缺损评分（mNSS）法评价动物神经行为功能，氯化三苯基四氮唑（TFC）染色观察脑梗死体积，原位末端标记法（TUNEL）检测细胞凋亡，免疫组织化学和蛋白印迹法检测pERK1／2表达水平。结果与对照组比较，模型组和LPS组mNSS评分显著升高、神经功能缺损明显，而治疗组与U0126组较模型组与LPS组显著降低（P〈0．05）。TUNEL检测显示各组凋亡指数（ACI）为对照组（0．06±0．02）、模型组（0．27±0．03）、治疗组（0．07±0．02）、LPS组（0．26±0．03）和U0126组（0．09±0．05），治疗组和U0126组明显低于模型组和LPS组（／9〈0．05），接近正常对照组。免疫组化和WB检测显示，模型组pERK1／2水平最高，略高于LPS组，而治疗组与U0126组水平明显降低（P〈0．05）。结论脑缺血损伤后激活ERK1／2信号通路介导神经细胞凋亡，胡黄连苷Ⅱ可能通过降低ERK1／2磷酸化水平，抑制神经细胞凋亡而发挥其神经保护作用。Objective To explore the neuroprotective effect and mechanism of picroside Ⅱ on ERK1/2 signal transduction pathway after cerebral ischemia injury in rats. Methods The focal cerebral is±chemic models were established by inserting a monofilament threads into middle cerebral artery occlusion （MCAO） in 100 Wistar rats and treated by injecting picroside Ⅱ （20 mg/kg） intraperitoneally. The neu- robehavioral function was evaluated by modified neurological severity score points （mNSS） test. The cerebral infarct volume was measured by tetrazolium chloride （TIC） staining. The apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay. The expression of pERK1/2 in cortex was determined by the immunohistochemistry （IHC） and Western Blot （WB）. Results mNSS test showed that severe neurological dysfunction was found in model and LPS groups, and the scores of mNSS were significantly increased; meanwhile the scores of mNSS in treatment group and U0126 group were signifi- cantly lower than that in model and LPS groups （P〈0.05）. TUNEL assay showed that the apoptotic cell indexes （ACI） in different groups were （ 0.06 ± 0.02）, （ 0.27± 0.03 ）, （ 0.07 ±0.02）, （ 0.26 ± 0.03 ） and （ 0.09± 0.05） ,and the ACI in treatment and U0126 groups was obviously lower than that in model and LPS groups （P〈0.,05）. With IHC and WB, pERK1/2 level in model group was the highest, which was slightly higher than that of LPS group, and pERK1/2 expression in treatment and U0126 groups was significantly decreased com- pared with that in model and LPS groups （P〈0.05） .Conclusion The activation of ERKI/2 by cerebral ischemia could induce the cell apoptosis. Picroside II might reduce cell apoptosis by inhibiting the activation of ERK1/2 in ischemic brain injury.

关 键 词：胡黄连苷Ⅱ 脑缺血 凋亡 ERK1/2 大鼠 

分 类 号：R285.5[医药卫生—中药学]