胡黄连苷Ⅱ对脑缺血损伤后COX-2表达的影响及意义

摘要

Objective To explore the neuroprotective effect and mechanism of picrosideⅡon the expression of COX-2 after cerebral ischemia injury in rats. Methods The focal cerebral ischemic models were established by inserting a monofilament threads into middle cerebral artery occlusion (MCAO) in 140 Wistar rats. All rats were randomly divided into control group, model group, picroside group, LPS group and U0126 group, each group contained 6 h, 12 h and 24 h subgroup. The neurobehavioral function was evaluated by modified neurological severity score points (mNSS) test. The apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression of COX-2 in cortex was determined by Western Blot. Results In model group, the neurobehavioral function score, apoptotic cell index, the expression of COX-2 increased significantly than those in control group. In picroside group and U0126 group, the number of apoptotic cells and the expression of COX-2 decreased significantly than those in model group. In LPS group, at 6 h the COX-2 expression were much higher than that in model group, later recovered slightly. Conclusions Picroside Ⅱ can down-regulate the expression of COX-2 to protect the neuron from the apoptosis and inflammation after MCAO in rats.%目的：探讨胡黄连苷Ⅱ对脑缺血损伤后COX-2表达的影响及其神经保护作用机制。方法应用线栓法建立大鼠大脑中动脉闭塞（MCAO)模型，按照随机对照原则，动物分为对照组、模型组、胡黄连苷组、 LPS组和U0126组，每组再分为缺血6 h、12 h和24 h三个亚组。改良的神经功能评分（mNSS)法评价大鼠神经行为功能；原位末端标记（TUNEL)法检测细胞凋亡；蛋白免疫印迹法检测脑组织COX-2表达水平。结果大鼠脑缺血损伤后，随着时间的延长模型组大鼠神经功能评分升高，皮质区神经凋亡增多， COX-2蛋白表达增强。胡黄连苷组和U0126组大鼠皮质区神经细胞凋亡和COX-2表达较模型组明显降低， LPS组大鼠早期神经细胞凋亡细胞与COX-2表达水平较高，但后期COX-2表达水平有所下降，损伤略有恢复。结论胡黄连苷Ⅱ可能通过降低COX-2通路的活化，抑制脑缺血后神经细胞凋亡和炎性反应而保护神经系统。