缺氧缺血再灌注脑损伤新生大鼠早期核因子κB信号通路的变化  

Change of Nuclear Factor-κB Signaling Pathway Alteration in Neonatal Rats with Early Hypoxic-Ischemic Reperfusion Brain Damage

作　　者：张士发[1] 周名雄[1] 睢燕[1] 

机构地区：[1]皖南医学院弋矶山医院儿科,安徽芜湖241001

出　　处：《实用儿科临床杂志》2009年第14期1080-1082,共3页Journal of Applied Clinical Pediatrics

摘　　要：目的探讨缺氧缺血再灌注脑损伤(HIRBD)新生大鼠早期核因子κB(NF-κB)信号通路相关基因的表达变化。方法24只7日龄新生SD大鼠,雌雄各半,随机分成3组:正常对照组(A组)、缺氧缺血再灌注2h组(B组)及缺氧缺血再灌注4h组(C组),每组8只。断头取其脑海马,抽提总RNA。运用基因芯片及生物信息分析技术检测NF-κB信号通路中相关信号分子的表达。结果与A组比较,B组单核细胞趋化蛋白2、双特异性磷酸酶1、FBJ成骨肉瘤癌基因(Fos)和Toll样受体9(Tlr9)基因表达上调,半胱氨酸天门冬氨酸蛋白酶1、8(Caspase-1、8)、促分裂原活化蛋白激酶激酶6、细胞外信号调节蛋白激酶和Ras基因同源基因家族成员a基因表达下调。C组Fos、IL-1β和Tlr6基因表达均上调,Caspase-1、细胞外基质蛋白1、溶血磷脂酸相关的G蛋白偶联受体、黏膜相关淋巴样组织转运蛋白1、NF-κB抑制因子激酶epsilon和Ras基因同源基因家族成员c基因表达均下调。结论在新生大鼠HIRBD早期阶段,主要通过Tlrs诱导NF-κB激活,从而调控下游炎性反应、细胞凋亡及细胞增殖相关基因的表达,参与HIRBD的病理生理过程。Objective To explore the changes of genes associated with the nuclear factor of kappa B （ NF - κB ） signaling pathway in neonatal rats with early hypoxic -ischemic reperfusion brain damage （HIRBD）. Methods Twenty -four SD rats at age of 7 days,with male to female of 12 ： 12, were randomized into normal control group（ group A, n = 8 ）, hypoxic -ischemia reperfusion for 2 h（ group B, n = 8 ） and hypoxic - ischemia reperfusion for 4 h （ group C, n = 8 ）. The tissues of hippocampus were taken for complete RNA extraction. Gene chip inspection and biological signal analysis technique were used to detect the expression of 113 involved signal molecules of NF - κB pathway. Resuits Compared with group A, the up - regulated expression was found in Chemokine （ C - C motif） ligand 2, Dual specificity phosphatase 1, FBJ osteosareoma oncogene（Fos） and Toll - like receptor 9. Whereas the expressions of Caspase - 1,8, Mitogen - activated protein kinase kinase 6, Mitogen activated protein kinase 3 and Ras homolog gene family member a from Ras - gene famimly was found down - regulated in group B. The up - regulated expression was in Fos, IL - 1β and Toll - like receptor 6, but that of down - regulation was found in Caspase - 1, Extracellular matrix protein 1, Lysophosphatidic Acid G - protein - coupled receptor 2, Mucosa associated lymphoid tissue lymphoma translocation gene 1, Inhibitor of kappa B kinase epsilon and Ras homolog gene family member c. Conclusions At the early stage of HIRBD, the Toll - like receptors may induce NF - κB activation,leading to the coordinated induction of multiple genes, which is involved in inflammatory, apoptosis and cell proliferation. Genes induced by NF - κB are responsible for the physiopathological process of early brain damage in neonatal rats with HIRBD.

关 键 词：缺氧缺血再灌注 核因子ΚB 信号通路 基因芯片 

分 类 号：R722.1[医药卫生—儿科]