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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 investigate the expression changes of early nuclear factor kappa B (NF-κB) signaling pathway in neonatal rats with hypoxic-ischemia-reperfusion brain injury (HIRBD). Methods Twenty-four newborn SD rats of 7 days old were randomly divided into 3 groups: normal control group (A), hypoxia-ischemia reperfusion 2h group (B) and hypoxia-ischemia reperfusion 4h group Group C), 8 in each group. Take the decapitated hippocampus, extract the total RNA. Gene chips and bioinformatics analysis were used to detect the expression of related signal molecules in NF-κB signaling pathway. Results Compared with group A, the expression of monocyte chemoattractant protein 2, bispecific phosphatase 1, FBJ osteosarcoma oncogene (Fos) and Toll - like receptor 9 (Tlr9) gene were up - regulated in group B, Caspase-1, 8, mitogen-activated protein kinase kinase 6, extracellular signal-regulated protein kinase and Ras gene family member a gene expression down regulation. The expressions of Fos, IL-1β and Tlr6 genes in group C were up-regulated. The expressions of caspase-1, extracellular matrix protein 1, lysophosphatidic acid-related G protein-coupled receptor, mucosa-associated lymphoid tissue transport protein 1, NF-κB inhibitor Genes were downregulated in members of the kinase epsilon and Ras gene families. Conclusion In the early stage of neonatal HIRBD, NF-κB activation is mainly induced by Tlrs to regulate the expression of downstream inflammatory response, apoptosis and cell proliferation-related genes and participate in the pathophysiological process of HIRBD.