海风藤酮对老龄大鼠局灶性脑缺血DNA损伤修复相关基因GADD45表达的影响  

Effect of Kadsurenone on the expression of DNA damage and repair related gene: GADD45 following focal cerebral ischemia in aged rats

作　　者：徐广润[1] 张东君[2] 杨渊[1] 张苏明[1] 方思羽[1] 迟兆富[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科,湖北武汉430030 [2]山东大学齐鲁医院神经内科,山东济南250012

出　　处：《山东大学学报（医学版）》2006年第2期146-149,160,共5页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金重点资助项目(No.39730170);面上项目(No.39770810)

摘　　要：目的:观察老龄大鼠局灶性脑缺血后DNA损伤修复相关基因GADD45表达的规律,探讨海风藤酮对神经细胞凋亡及GADD45表达的影响。方法:采用26月龄Wistar大鼠,经光化学诱导局灶性脑缺血后应用海风藤酮进行干预,观察不同时间和空间状态下GADD45蛋白表达的改变,同时运用TUNEL染色观察神经细胞的凋亡现象。结果:缺血4h组,在缺血中心区可见少许GADD45反应阳性细胞,而缺血周边区GADD45反应阳性细胞大量表达,较对照组差异有统计学意义(P<0.05)。缺血24h组,周边区GADD45表达较缺血4h有所降低,但仍高于假手术组(P<0.05),至缺血5d时,周边区GADD45表达较假手术组无明显差异。海风藤酮治疗组,缺血周边区TUNEL阳性细胞数较假手术组增多(P<0.05),但较对照组减少(P<0.05),而GADD45表达阳性细胞数较对照组增多(P<0.05),与假手术组比较增多(P<0.01)。结论:海风藤酮可有效保护缺血神经细胞,同时可以上调DNA修复基因GADD45的表达,减小DNA损伤的程度。Objective： To observe the expression of DNA damage and repair gene： GADD45 following cerebral ischemia in aged rats, and to investigate the effects of Kadsurenone on the expression of GADD45 and neuronal cell apoptosis. Methods： Wistar rats of 26-month-old with focal cerebral ischemia were administered herb Kadsurenone. The change of GADD45 protein expression was determined with immunohistochemistry, and the neuronal cell apoptosis with TUNEL staining techniques. Results： Few GADD45 response positive cells existed in the core of ischemic area 4 hours after ischemia, but a great deal expressed in the peripheral area, which was significantly different from the control group （P〈0.05）. GADD45 response positive cells at 24 hours were fewer than those at 4 hours, but higher than those in pseudo-surgery group（P〈 0.05）. TUNEL positive cells in herb Kadsurenone group increased compared with pseudo-surgery group （P〈 0.05）, but decreased compared with 24-hour ischemia control group （P〈0.05）. GADD45 positive cell of herb kadsurenone group increased compared with control group （P〈0.05） and pseudo-surgery group （P〈0.01）. Conclusions： Kadsurenone, an inhibitor of PAF has protective effect on cerebral ischemia, and it can decrease the extent of DNA damage and up-regulate the expression of GADD45, a DNA repair gene.

关 键 词：脑缺血 基因 GADD45 海风藤酮 DNA修复 

分 类 号：R743[医药卫生—神经病学与精神病学]