Faculty of Life Sciences, Kharazmi University, Tehran, Iran.
Faculty of Life Sciences, Kharazmi University, Tehran, Iran.
Brain Res Bull. 2021 Apr;169:205-213. doi: 10.1016/j.brainresbull.2021.01.013. Epub 2021 Jan 27.
The increase in some factors following cerebral ischemia, especially Matrix metalloproteinase (MMPs) and inflammatory factors lead to blood-brain barrier (BBB) damages, edema and neuronal death. Previous studies have shown that these molecules are miRNA-149-5p (miR-149) and Coenzyme (Co) Q10 targets. Therefore, in this study, the effect of mimic of miRNA-149-5p (mimic miR) and CoQ10 on the expression of metalloproteinase 1 and 2 and inflammatory cytokines following injury caused by cerebral ischemia is investigated. Cerebral ischemia was modeled by Middle Cerebral Artery Occlusion (MCAO). Male Wistar rats were randomly divided into 6 groups: sham (without surgery and treatment), control (MCAO), negative control (NC): MCAO + scrambled miR, vehicle: MCAO + Ethanole, first treatment: MCAO + mimic miR, second treatment: MCAO + Q10. Each group was divided into 6 subgroups to evaluate neurological defects, the volume of tissue damage using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, blood-brain barrier permeability using cerebral Evans Blue (EB) staining, edema by measuring the percentage of brain water, MMP-2,9 mRNA and miR-149-5p levels using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the levels of IL-6 and TNF-α proteins using ELISA. The data obtained from this study showed that the use of mimic miR and Q10 increased the level of miR-149, decreased the extent of neurological defects and tissue damage, increased BBB integrity, decreased brain water percentage and also decreased the level of inflammatory cytokines and MMPs. It seems that the use mimic of miRNA-149-5p and Q10 can have a protective effect on the brain by reducing MMPs and inflammatory factors following cerebral ischemia and this could lead to a new treatment strategy to reduce the complications of cerebral ischemia.
脑缺血后某些因素的增加，尤其是基质金属蛋白酶（MMPs）和炎症因子导致血脑屏障（BBB）损伤、水肿和神经元死亡。先前的研究表明，这些分子是 miRNA-149-5p（miR-149）和辅酶（Co）Q10 的靶标。因此，在这项研究中，研究了 miRNA-149-5p 的模拟物（mimic miR）和 CoQ10 对脑缺血损伤后金属蛋白酶 1 和 2 以及炎症细胞因子表达的影响。通过大脑中动脉闭塞（MCAO）建立脑缺血模型。雄性 Wistar 大鼠随机分为 6 组：假手术组（无手术和治疗）、对照组（MCAO）、阴性对照组（NC）：MCAO+ scrambled miR、载体组（MCAO+乙醇）、第一治疗组（MCAO+ mimic miR）、第二治疗组（MCAO+ Q10）。每组又分为 6 个亚组，以评估神经缺陷、2,3,5-三苯基氯化四氮唑（TTC）染色评估组织损伤体积、脑伊文思蓝（EB）染色评估血脑屏障通透性、脑水百分比测量评估脑水肿、定量实时聚合酶链反应（qRT-PCR）评估 MMP-2、9 mRNA 和 miR-149-5p 水平、酶联免疫吸附试验（ELISA）评估 IL-6 和 TNF-α 蛋白水平。本研究获得的数据表明，使用 mimic miR 和 Q10 增加了 miR-149 的水平，降低了神经缺陷和组织损伤的程度，增加了 BBB 的完整性，降低了脑水百分比，也降低了炎症因子和 MMPs 的水平。似乎使用 miRNA-149-5p 的模拟物和 Q10 可以通过降低脑缺血后 MMPs 和炎症因子来对大脑产生保护作用，这可能为减少脑缺血并发症提供一种新的治疗策略。
