（ 1、華中科技大學同濟醫學院法醫學系，武漢 430030； 2、華中科技大學 同濟醫學院法醫學系 湖北武漢 430030； ）
摘要： 目的 應用微陣列基因芯片技術檢測創傷性腦損傷大鼠傷后1天、3天、5天的大腦海馬microRNA表達變化,分析差異表達的海馬microRNA對腦損傷后認知功能障礙的可能作用機制。方法 SD大鼠行大腦單側控制性皮層撞擊損傷建立創傷性腦損傷動物模型（速度4米/秒，持續150毫秒，打擊深度3毫米）。在傷后1天、3天、5天處死大鼠分離致傷側大腦海馬組織，應用基因芯片技術分析海馬microRNA的表達情況。結果 由基因芯片分析得到分層聚類圖，與對照組相比，在205個microRNA中，傷后1d組有41個microRNA表達上調1.5倍以上，31個microRNA表達下調1.5倍以上；傷后3d組有81個microRNA表達上調1.5倍以上，11個microRNA表達下調1.5倍以上；傷后5d組有52個microRNA表達上調1.5倍以上，41個microRNA表達下調1.5倍以上。共有17個microRNA在三個損傷時間點均出現差異性表達，其中miR-142-3p和miR-221可能在腦損傷的病理生理學過程中起到關鍵作用。結論 傷后不同時間點大鼠海馬microRNA的表達具有不同時序性，推測其在海馬應對顱腦損傷的過程中發揮著特定作用。其中，miR-142-3p和miR-221有可能作為潛在的生物學標記物在臨床法醫學上用以評估創傷性腦損傷，并為損傷相關的認知功能障礙奠定實驗研究基礎。
SUN Tingyi1,， LIU Zilong2,*， LIU Liang2,， CHEN Xiaorui2,， ZHAO Lili2,， QU Guoqiang2,
（ 1、Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, WuHan 430030； 2、Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030； ）
Abstract： Objectives To descript the changes in expression of microRNAs in the hippocampus of rats at 1 day, 3 days and 5 days following traumatic brain injury (TBI) by microarray technique, and investigate the possible cellular activities that are regulated by microRNAs which differentially expressed in the hippocampus, that may contribute to TBI-induced cognitive impairment. Methods Adult SD rats received a single controlled cortical impact (CCI) injury using an electromagnetic piston at a velocity of 4 m/sec, duration of 150 ms and depth of 3 mm. The ipsilateral hippocampus was harvested for the subsequent microarray assays at three time points post-injury: 1 day, 3 days and 5 days, respectively. We characterize the microRNA expression profile in rat hippocampus compared with sham group using the Significance Analysis of Microarrays analysis. Results We got a dendrogram of a Hierarchical Clustering analysis of the result. Totally 205 microRNAs were identified which were up-/down-regulated more than 1.5 times. At 1 d post-injury, 41 microRNAs were up-regulated more than 1.5 times, and 31 microRNAs were down-regulated more than 1.5 times; at 3 d post-injury, 81 microRNAs were up-regulated more than 1.5 times, and 11 microRNA s were down-regulated more than 1.5 times; at 5 d post-injury, 52 microRNAs were up-regulated more than 1.5 times, and 41 microRNAs were down-regulated more than 1.5 times. Furthermore, we revealed 17 microRNAs which were changed at all three time points post-injury, the notable two microRNAs were miR-142-3p and miR-221, which could involve in many pathophysiological processes. Conclusions Our microarray-based bioinformatics analysis has showed that microRNAs in rat hippocampus have different expression levels at various time points post-injury, suggesting it is likely an active approach for cells to cope with injury through modulating microRNA expression, and microRNAs play key roles in the pathological courses after injury and work collaboratively like a complicated gene expression network. MiR-142-3p and miR-221 may be used as potentially biological markers for TBI assessment, and thus make some improvements in exploratory research for TBI-related cognitive disorder.
Keywords： forensic clinical medicine; microRNA; microarray; hippocampus; traumatic brain injury
作者簡介： SUN Tingyi,(1985-), female, PhD, forensic pathology and clinical forensic medicine （孫婷怡，1985-，女，博士研究生，研究方向為法醫病理學和法醫臨床學 ）
通信聯系人： LIU Zilong (1976-), male, PhD, Lectuer, clinical forensic medicine；（劉子龍，1976-，男，博士，講師，研究方向為臨床法醫學）