Activation of nuclear factor-κB in the brain after experimental subarachnoid hemorrhage and its potential role in delayed brain injury.
Activation of nuclear factor-κB in the brain after experimental subarachnoid hemorrhage and its potential role in delayed brain injury.
复制标题
DOI：
10.1371/journal.pone.0060290
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhou ML
中科院分区：
文献类型：
--
作者：
You WC;Wang CX;Pan YX;Zhang X;Zhou XM;Zhang XS;Shi JX;Zhou ML
据报道，蛛网膜下腔出血（SAH）后的脑损伤与炎症有关。核因子-κB （NF-κB）是炎症基因的关键转录调节因子。本研究通过腹腔注射NF-κB抑制剂吡咯烷二硫代氨基甲酸酯（PDTC），研究NF-κB在SAH后迟发性脑损伤中的作用。55只家兔随机分为5组：对照组；SAH组分为SAH第3、5、7天组（各组分别于SAH后第3、5、7天处死）；PDTC组（每组n = 11）。采用EMSA检测NF-κB dna结合活性。RT-PCR检测肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、细胞间粘附分子(ICAM)-1 mRNA表达水平。TUNEL检测脱氧核糖核酸片段，免疫组织化学检测p65免疫活性。我们的结果显示，在SAH后NF-κB被激活，特别是在第3天和第5天。在神经元中检测到激活的p65。腹腔注射PDTC可抑制NF-κB dna结合活性。在SAH后第5天，脑组织中TNF-α、IL-1β和ICAM-1 mRNA水平升高，而PDTC组抑制了这些水平。与第5天的SAH组相比，PDTC组tunel阳性细胞数量也明显减少。这些结果表明，SAH后神经元活化的NF-κB在调节脑内炎症基因的表达中起重要作用，最终导致脑延迟损伤。
It has been reported that inflammation is involved in brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-κB (NF-κB) is a key transcriptional regulator of inflammatory genes. Here, we used pyrrolidine dithiocarbamate(PDTC), an inhibitor of NF-κB, through intracisternal injection to study the role of NF-κB in delayed brain injury after SAH. A total of 55 rabbits were randomly divided into five groups: the control group; the SAH groups including Day-3, 5, and 7 SAH groups (the rabbits in these groups were sacrificed at 3, 5, 7 days after SAH, respectively); and the PDTC group (n = 11 for each group). Electrophoretic mobility shift assay (EMSA) was performed to detect NF-κB DNA-binding activity. The mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and intercellular adhesion molecule (ICAM)-1 were evaluated by RT-PCR analysis. Deoxyribonucleic acid fragmentation was detected by TUNEL and p65 immunoactivity was assessed by immunohistochemistry. Our results showed the activation of NF-κB after SAH, especially at day 3 and 5. The activated p65 was detected in neurons. NF-κB DNA-binding activity was suppressed by intracisternal administration of PDTC. Increased levels of the TNF-α, IL-1β, and ICAM-1 mRNA were found in the brain at day 5 after SAH, and which were suppressed in the PDTC group. The number of TUNEL-positive cells also decreased significantly in the PDTC group compared with that in the Day-5 SAH group. These results demonstrated that the activated NF-κB in neurons after SAH plays an important role in regulating the expressions of inflammatory genes in the brain, and ultimately contributes to delayed brain injury.
登录
查看更多内容
DOI：
10.1073/pnas.92.20.9077
发表时间：
1995-09-26
影响因子：
11.1
作者：
GUERRINI, L;BLASI, F;DENISDONINI, S
通讯作者：
DENISDONINI, S
影响因子：
4.1
作者：
MATHIESEN, T;ANDERSSON, B;VONHOLST, H
通讯作者：
VONHOLST, H
影响因子：
56.9
作者：
AUPHAN, N;DIDONATO, JA;KARIN, M
通讯作者：
KARIN, M
影响因子：
4.1
作者：
Matz, PG;Sundaresan, S;Weinstein, PR
通讯作者：
Weinstein, PR
影响因子：
4.8
作者：
Aoki, Tomohiro;Kataoka, Hiroharu;Miyamoto, Susumu
通讯作者：
Miyamoto, Susumu