miR-146a通过靶向调控TLR4减轻脊髓缺血再灌注大鼠损伤  

miR-146a reduces injury of spinal cord ischemia reperfusion by targeting TLR4 in rats

作　　者：贾慧[1] 方波[1] 强子耘 张馨心 马虹[1] JIA Hui;FANG Bo;QIANG Zi-yun;ZHANG Xin-xin;MA Hong(Department of Anesthesiology,First Hospital Affiliated of China Medical University,Shenyang 110001;Department of Anesthesiology,4th People's Hospital of Shenyang,Shenyang 110031;2016 grade,First Clinical Medical Institute of Jinzhou Medical University,Jinzhou 121000,China)

机构地区：[1]中国医科大学附属第一医院麻醉科,辽宁沈阳110001 [2]沈阳市第四人民医院,辽宁沈阳110031 [3]锦州医科大学第一临床学院,辽宁锦州121000

出　　处：《解剖科学进展》2021年第3期337-340,共4页Progress of Anatomical Sciences

基　　金：国家自然科学基金(81771342,81971152);辽宁省自然基金指导项目(2019-ZD-0742)。

摘　　要：目的检测miR-146a在脊髓缺血再灌注(IR)大鼠脊髓组织的表达情况,探索miR-146a对IR大鼠炎症蛋白表达和神经功能影响的潜在机制。方法 SD大鼠通过主动脉弓夹闭14min建立IR模型,通过鞘内注射miR-146a的mimics质粒构建miR-146a过表达模型,随机分为Sham组(假手术组),IR组(缺血组)和mimic组(miR-146a过表达组)。qRT-PCR评估损伤节段脊髓组织miR-146a表达水平;Western blot检测TLR4和IRAK1蛋白表达;Tarlov评分对大鼠进行下肢神经功能评估;对miR-146a和TLR4进行生物信息学预测。结果与Sham组相比,IR组miR-146a表达降低,TLR4和IRAK1蛋白表达增高,Tarlov运动功能评分降低;和IR组相比,mimic组TLR4和IRAK1蛋白表达下调,Tarlov运动功能评分增高;生物信息学预测显示miR-146a和TLR4存在结合位点。结论 miR-146a可作为IR潜在的诊断标记物,miR-146a可能通过靶向TLR4蛋白减轻大鼠脊髓缺血再灌注的炎性损伤。Objective To explore the expression of miR-146a in the spinal cord tissue of IR rats, and to explore the effect of miR-146a on the expression of inflammatory proteins and neurological function in IR rats and its possible mechanism. Methods SD rats were clipped the aortic arch for 14 minutes to establish a rat spinal cord ischemiareperfusion(IR) model, and the miR-146a overexpression model was constructed by intrathecal injection of the mimics plasmid of miR-146a. Therats were randomly divided into Sham group(sham operation group), IR group(ischemia reperfusiongroup) and mimic group(miR-146a overexpression group). The expression level of miR-146a in injured spinal cord tissue was evaluated by qRT-PCR, and the protein expression of TLR4 and IRAK1 weredetected by Western Blot. The Tarlov score was used to asessthelimbfunctionofratsand bioinformatics predictions wasperformedfor miR-146a and TLR4. Results Compared with the Sham groups, the expression of miR-146a in the IR groups was decreased, the protein expression of TLR4 and IRAK1 was increased, alongwith the decreased Tarlov score. Compared with the IR groups, the mimicsdown-regulated the expression of TLR4 and IRAK1 proteins and increased the Tarlov score. It is predicted that thereisabidingsitesbetweenmiR-146a and TLR4 by bioinformatics. Conclusion miR-146a couldbe used as a potential diagnostic marker for IR, andmiR-146a may be involved in spinal cord ischemiareperfusion injury by targeting TLR4 protein.

关 键 词：MIR-146A 脊髓缺血再灌注损伤 TLR4 IRAK1 

分 类 号：R651.2[医药卫生—外科学]