大鼠脑出血急性期核因子Nrf2信号通路表达变化及其与继发性脑损伤的关系  

Relationship between Nrf2 pathway expression and secondary brain injury during acute stage of cerebral hemorrhage in rats

作　　者：尚寒冰[1] 张卫峰[1] 赵卫国[1] 杨德华[2] 李厅 

机构地区：[1]上海交通大学医学院附属瑞金医院神经外科,200025 [2]中国科学院上海生命科学研究院上海交通大学医学院健康科学研究所

出　　处：《中国脑血管病杂志》2013年第2期79-83,共5页Chinese Journal of Cerebrovascular Diseases

摘　　要：目的观察大鼠脑出血(ICH)急性期不同时间点核因子Nrf2信号通路相关因子的表达与继发性脑损伤的关系。方法将120只大鼠随机分为出血组和假手术组,每组60只。采用自体血立体定向注入大脑基底核区,建立大鼠ICH模型,根据ICH后不同时间点,将大鼠随机分为2、8、24 h,3、5、10 d组,各时间点设相应假手术组,每组10只。分别于造模后2、8、24 h,3、5、10 d,检测Nrf2及其下游基因的mRNA及蛋白水平表达的变化,并在相应时间点行神经行为学评价及脑含水量的测定。结果①从ICH后24 h开始,出血组大鼠的前肢抬起的比例均低于假手术组,出血组的右向转角比例均高于假手术组,差异均有统计学意义,P<0.05。②在ICH后24 h,3、5 d,出血组的脑含水量高于假手术组,差异有统计学意义,P<0.05。出血组的脑含水量在3 d达到高峰,为(86.9±5.4)%,此后逐渐降低。③与假手术组比较,Nrf2 mRNA在ICH后2 h至5 d均高于假手术组,2 h达到高峰,差异有统计学意义。Nrf2下游基因血红素加氧酶(HO)、谷胱甘肽-S-转移酶α1(GST-α1)、谷胱甘肽(GSH)及硫氧还蛋白(TRX)mRNA表达亦有不同程度的升高。其中HO-1mRNA表达上调最为显著,ICH后2 h至5 d均高于假手术组,3 d时达高峰,差异有统计学意义。④与假手术组比较,Nrf2蛋白在ICH后2 h至5 d均高于假手术组,24 h达到高峰,相对表达量为0.39±0.05,差异有统计学意义。HO-1蛋白在ICH后8 h至10 d均高于假手术组,3 d达到高峰,相对表达量为0.99±0.08,差异有统计学意义。结论核因子Nrf2信号通路在大鼠ICH急性期被激活,影响下游基因的表达,其中HO-1表达变化与神经行为学、脑含水量变化趋势相近,可能在反映ICH继发性脑损伤程度方面具有重要意义。Objectives To observe expression changes of nuclear transcription factor Nrirf2 pathway during acute stage of intracerebral hemorrhage （ICH） in rats and to investigate the antioxidative mechanism of Nrt2 in the secondary brain injury after ICH. Methods 120 rats were divided into either an ICH group or a sham operation group （n=60 in each group）. A rat ICH model was induced by stereotaxic injection of autologous blood into the basal ganglia. According to the different time points after ICH, the rats were ran- domly divided into 2h, 8h, 24h, 3d, 5d, and 10d subgroups（n=10 in each group） and a sham opera- tion subgroups . The expression changes of Nrf2 and its downstream genes on mRNA and protein levels were detected at each time point after modeling. The neurological behavior test and determination of brain water content were performed at corresponding time points. Results ①From 24 h after ICH, the proportion of forelimb raise in the ICH group was lower than that in the sham operation group; the proportion of turn right angle in the ICH group was higher than that in the sham operation group. The differences were statistically significant （P〈0.05）. ②The brain water content in the ICH group was higher than that in the sham operation group at 24 h, day 3 and 5 after ICH. The brain water content in the ICH group reached the peak （86.9 %±5.4 % ） at day 3, and then decreased gradually.③Compared to the sham operation group, the Nrf2 mRNA levels were higher than the sham operation group from 2 h to day 5 after 1CH. The differences were statistically significant. The Nrf2 downstream genes such as heme oxygenase （HO）, glutathione S-transferase cd （GST-α1）, glutathione （GSH）, and thioredoxin （TRX） expression increased to various degrees,the HO-1 mRNA expression was most significantly upregulated, and it was higher than the sham operation group from 2 h to day 5 after ICH. It reached the peak at day 3. ④Compared to the sham operation group, the Nrf2 protein was higher than that i

关 键 词：脑出血 脑损伤 大鼠 氧化应激 核转录因子 

分 类 号：R743.3[医药卫生—神经病学与精神病学]