中文摘要：

目的探讨创伤性颅脑损伤后基因表达变化及颅脑损伤后的神经保护机制。方法应用细胞损伤仪（CICⅡ）建立细胞牵张损伤模型，各项参数分别设定为：脉冲时间为50ms、计量阀门压力为0．165MPa，使气体脉冲压为（O．021±0．001）MPa。采用Trizol法提取损伤组和对照组的细胞RNA，进行mRNA测序，并对差异表达基因进行基因本体分析和生物信息分析软件（IPA）进行信号通路分析，并通过实时荧光定量PCR（qPCR）对定量结果进行验证。结果在2个样本中，分别得到1431万个和1551万个读段，鉴定出15018个基因在2个样本中均有表达。差异表达基因有1424个，相较于对照组，损伤组上调1198个基因，下调226个基因（P〈0．01）。与对照组相比，损伤组缺氧诱导因子10[抗体（HIF-1α）及ZFP36表达均下调，并发现了TBI后13个差异表达基因，构成了以HIF-1α和ZFP36为中心的调控网络。在该网络中，HIF-1α受EGLN2和ZFP36的调控，并与PER1相互作用，同时调控多个下游基因的表达，如H2AFX、ABCF2和SLC39A7。结论颅脑损伤12h，HIF-1α在mRNA水平分别受到ZFP36、HNRNPD和EGLN2的调控而下调，并进一步调节H2AFX的表达，进而阻止神经细胞凋亡，促进了神经细胞的损伤修复。

英文摘要：

Objective To investigate the changes of gene expression after traumatic brain injury （TBI） and the neuroprotective znechanism after TBI. Methods A cell stretch injury model was induced by using a cell injury controller Ⅱ（CIC Ⅱ）. Each parameter was set as pulse time 50 ms and metering valve pressure 0. 165 MPa. The gas pulse pressure was 0. 021 ± 0. 001 MPa. The cell RNAs were extracted by using Trizol reagent in the injury group and the control group, and then the mRNA sequencing was performed. The gene ontology of the differentially expressed genes was analyzed and the ingenuity pathway analysis （IPA） software was used to conduct signaling pathway analysis. The quantitative results were validated by qPCR. Results There were 14 310 000 and 15 510 000 reads were obtained respectively in the two samples, and 15 018 genes expressed in the two samples were identified. There were 1 424 differentially expressed genes. Compared to the control group, 1 198 genes were up-regulated and 226 genes were down-regulated in the injury group （P 〈 0. 01 ）. Compared with the control group, HIF-1α and ZFP36 expression levels were down-regulated in the injury group and 13 differentially expressed genes after TBI were found and constituted a regulatory network with HIF-1α and ZFP36 as the center. In this network, HIF-1α was regulated by EGLN2 and ZFP36, and interacted with PER1, and regulated the expression of multiple downstream genes at the same time, such as H2AFX, ABCF2, and SLC39A7. Condusions When the injury lasted for 12 hours, HIF-1α at the mRNA level was down regulated by ZFP36, HNRNPD, and EGLN2, respectively, and further regulated the expression of H2AFX, and then prevented the nerve cells from apoptosis, and promoted the repair of nerve cell injury.