Abstract:

Objective To investigate the relationship between CUR and the expression of Notch 1 and NF-κB, and evaluate the neuroprotection of CUR in rat permanent middle cerebral artery occlusion (MCAO). Methods A total of ninety-three male, Sprague-Dawley rats were subjected to MCAO. Among which, sixty-three rats were used to investigate the relationship between CUR and the expression of Notch 1 and NF-κB after cerebral ischemia, and 30 rats were used to detect the effect of CUR in the acute phase of ischemic stroke. Neurological deficit, brain water content and infarct sizes were measured at 48 h after MCAO. Immunohistochemistry and Western blot were used to analyze the expression of Notch 1 and NF-κB. Results Compared with sham group, the expression of Notch 1 was up-regulated at early stage after cerebral ischemia. CUR down-regulated the expression of Notch 1 and NF-κB, and the inhibition effect lasted at least 72 hours after MCAO (P <0.05). Compared with vehicle-control group, CUR dramatically improved neurological deficit at 48 h (P <0.05), reduced brain water content [(80.42±9.00)% vs (83.71±7.00)% (P <0.05)] and infarct volume [(40.08±3.66)% vs (28.94±6.20)% (P <0.05)].Conclusion CUR protects the brain from damage caused by cerebral ischemia; this effect may be through down-regulating the expression of Notch 1 and NF-κB.

Key words: Cerebral ischemia; Curcumin; Inflammation; Notch 1; NF-κB

摘要：

目的 通过观察姜黄素（curcumin）对Notch 1及NF-κB表达的影响及脑含水量和梗死体积的变化，探 讨其对大脑中动脉梗死（middle cerebral artery occlusion，MCAO）模型大鼠的神经保护作用及机制。 方法 采用成年健康雄性Sprague-Dawl ey大鼠93只，随机分为假手术组（sham），溶剂对照组（vehi cl econtrol ），姜黄素组（CUR）。MCAO术后立即腹腔注射姜黄素溶液（80 mg/kg），溶剂对照组及假手术 组给予同体积含0.5 mol/L NaOH的0.01 PBS。根据不同时间点每组分为对照、3 h、6 h、12 h、24 h、48 h、 72 h共7个亚组，分别在相应时间点进行神经功能学评分，2～4分者纳入实验组。归组后将动物断头 处死，留取病变侧脑组织利用免疫组织化学法及Western blot观察Notch 1及NF-κB的表达。各组仅取 48 h一个时间点进行脑含水量测定及2%的2，3，5-三苯基四唑氮红（triphenyltetrazolium chloride，TTC） 染色观测梗死体积。 结果 CUR组降低Notch 1和NF-κB的表达，这种抑制效果至少持续至MCAO后72 h（P＜0.05）。与 vehicle-control组相比，CUR组在MCAO后48 h时即可显著改善神经功能缺损（P＜0.05），减少脑含水量 （[ 80.42±9.00）% vs（83.71±7.00）%（P＜0.05）]及梗死体积（[ 40.08±3.66）% vs（28.94±6.20）% （P＜0.05）]。 结论 姜黄素干预后，MCAO模型病变脑组织含水量降低，梗死体积减小，Notch 1和NF-κB表达水平 同步下调，推测姜黄素有脑保护作用，姜黄素可能通过抑制Notch 1和NF-κB的表达对缺血性脑组织 起到脑保护作用。

关键词: 缺血性脑血管病; 姜黄素; 炎症反应; Notch 1; NF-κ B