姜黄素通过调控Notch通路促进大鼠脑缺血后神经干细胞增殖和迁移  

Curcumin promotes proliferation and migration of neural stem cells in cerebral ischemic rats by regulating Notch signaling

作　　者：程建华[1] 刘双[1] 韩钊[1] 曹红[2] 杨金龙[1] 

机构地区：[1]温州医学院附属第一医院神经内科,浙江温州325000 [2]温州医学院附属第二医院麻醉科,浙江温州325000

出　　处：《中国病理生理杂志》2013年第5期878-882,共5页Chinese Journal of Pathophysiology

基　　金：浙江省中医药管理局科研项目(No.2010ZB093)

摘　　要：目的:观察姜黄素对大鼠局灶性脑缺血后室管膜下区(SVZ)神经干细胞(NSCs)增殖和迁移的影响,及其与Notch信号通路的相关性。方法:采用线栓法制备大鼠大脑中动脉缺血再灌注损伤模型,随机分成假手术组(sham)、缺血再灌注组(I/R)及姜黄素治疗组(I/R+curcumin)。动物在模型成功后1 h连续腹腔注射姜黄素7 d后处死。免疫荧光法检测各组梗死侧SVZ BrdU及BrdU/DCX标记NSCs的数目及迁移趋势。Western blotting方法检测各组Notch通路的中间产物Notch细胞内域(NICD)的表达。结果:I/R+curcumin组的大鼠梗死侧SVZBrdU及BrdU/DCX标记的NSC较I/R组显著增多(P<0.05),同时其较I/R组更广泛地分布在往病灶迁移的路径上。I/R+curcumin组较I/R组的NICD生成也增多(P<0.05)。结论:姜黄素能促进缺血性大鼠脑SVZ NSCs增殖和迁移,其机制可能是通过激活Notch信号通路产生的。AIM： To investigate the proliferation and migration of neural stem cells （NSCs） in the subventrie- ular zone （SVZ） on focal cerebral ischemia with curcumin treatment, and to explore the relationship between these effects and Notch signaling. METHODS： The animal model was established by an intraluminal suture method to induce middle cerebral artery occlusion in rats. The rats were randomly divided into sham group, cerebral ischemia/reperfusion （I/R） group, and I/R ＋ curcumin group. The animals were given curcumin for 7 d intraperitoneally. One hour after the model was successfully established, the rats were sacrificed. Immunofluorescence was used to label the NSCs by BrdU and BrdU/ DCX, and the migration tendency was observed. The expression of Notch intracellular domain （ NICD, the Notch signaling pathway intermediate product） was detected by Western blotting. RESULTS： Compared with I/R group, BrdU-positive and BrdU/DCX double positive cells in I/R ＋ curcumin group were significantly higher than those in I/R group （ P 〈 0. 05）, and more positive cells were on the way of migration to the ischemic lesion zone. The expression level of NICD in I/ R ＋ curcumin group was significantly higher than that in I/R group （ P 〈 0.05 ）. CONCLUSION ： Curcumin promotes NSC proliferation and migration in SVZ after focal cerebral ischemia. The possible mechanism may be that curcumin acti- vates Notch signaling.

关 键 词：姜黄素 局灶性脑缺血 神经干细胞 神经再生 NOTCH通路 

分 类 号：R743[医药卫生—神经病学与精神病学]