不同剂量姜黄素预先给药对全脑缺血再灌注大鼠海马p-CREB和PGC-1α表达的影响  

Effects of pretreatment with different doses of curcumin on expression of p.CREB and PGC-1α in hippocampus after global cerebral ischemia-reperfusion injury in rats

作　　者：叶莉莎[1] 黄晟[1] 周威[1] 李国政[1] 曹红[1] 连庆泉[1] 李军[1] 

机构地区：[1]温州医学院附属第二医院麻醉科,325027

出　　处：《中华麻醉学杂志》2010年第9期1099-1101,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（30772087）;浙江省自然科学基金（Y2100231）

摘　　要：目的 探讨不同剂量姜黄素预先给药对全脑缺血再灌注大鼠海马p-CREB和PGC-1α表达的影响.方法 雄性SD大鼠30o只,体重200～250 g,随机分为5组（n=60）：假手术组（S组）仅分离双侧颈总动脉但不阻断;全脑缺血再灌注组（IR组）采用四血管阻断法全脑缺血15 min再灌注的方法制备模型;低、中、高剂量姜黄素组（LC组、MC组和HC组）分别于缺血前1 h腹腔注射姜黄素30、100、300 mg/kg,S组和IR组腹腔注射等容积生理盐水.于再灌注2、6、24、72 h、7 d时各组随机取12只大鼠,分离海马,TUNEL法计数凋亡神经元,Western b1ot法检测海马p-CREB、PGC-1α蛋白的表达.结果 与S组比较,其余4组海马凋亡神经元数目增加,p-CREB、PGC-1α蛋白表达上调（P＜0.05）;与IR组比较,LC组和MC组凋亡神经元数目减少,LC组、MC组和HC组p-CREB、PGC-1α蛋白表达上调（P＜0.05）;与MC组比较,LC组和HC组凋亡神经元数目增加,p-CREB、PGC-1α蛋白表达下调（P＜0.05）.结论 姜黄素可通过上调p-CREB和PGC-1α的表达抑制海马神经元凋亡,从而减轻大鼠全脑缺血再灌注损伤.Abstract：Objective To explore the effects of pretreatment with different doses of curcumm on the expression of p-CREB and PGC-1α in hippocampus after global cerebral ischemia-reperfusion （IR） injury in rats.Methods Three hundred male SD rats weighing 200-250 g were randomly divided 5 groups （ n = 60 each）： sham operation group （group S）, IR group, low, median and high dose curcumin group （group LC, MC, HC）. Global cerebral ischemia was produced by occlusion of 4 vessels （cauterization of bilateral vertebral arteries and 15 min occlusion of bilateral common carotid arteries） according to the method described by Finkbeiner. Bilateral common carotid arteries were only exposed but not ligated in group S. Intraperitoneal curcumin 30, 100 and 300 mg/kg were injected at 1 h before ischemia in group LC, MC and HC respectively. Equal volume of dimethylsulfoxide （DMSO） was injected intraperitoneally in group S and IR. The rats were killed at 2, 6, 24 and 72 h and 7 d after reperfusion （12 at each time point）. Brains were immediately removed and hippocampus was isolated. The number of apoptosis neurons was counted using TUNEL. The expression of p-CREB and PG C-1α protein in hippocampus was detected by Western blot. Results The number of apoptosis neurons, p-CREB and PG C-1α protein expression were significantly higher at each time point in the other 4 groups than in group S （ P 〈 0.05）. The number of apoptosis neurons was significantly lower at T2-4 in group LC and MC, while p-CREB and PG C-Ⅰα protein expression wes significantly higher at T1-4 in group LC, MC and HC than in group IR （P 〈 0.05）. The number of apoptosis neurons was significantly higher, while p-CREB and PGC-1α protein expression was significantly lower at T2-4 in group LC and HC than in group MC （ P 〈 0.05）. Conclusion Curcumin can inhibit neuronal apoptosis in hippocampus and reduce global cerebral IR injury by up-regulating p-CREB and PG C-1α expression in rats and the effect was dose-related.

关 键 词：姜黄素 CAMP反应元件结合蛋白 反式激活因子类 再灌注损伤 细胞凋亡 海马 

分 类 号：R285.5[医药卫生—中药学]