*Women's Health in Neuroscience Program, Neuroscience and Experimental Therapeutics, Texas A&M College of Medicine, Bryan, TX 77807, U.S.A.
Clin Sci (Lond). 2014 Jul;127(2):77-89. doi: 10.1042/CS20130565.
Small non-coding RNA [miRNA (microRNA)] found in the circulation have been used successfully as biomarkers and mechanistic targets for chronic and acute disease. The present study investigated the impact of age and sex on miRNA expression following ischaemic stroke in an animal model. Adult (6 month) and middle-aged (11-12 months) female and male rats were subject to MCAo (middle cerebral artery occlusion) using ET-1 (endothelin-1). Circulating miRNAs were analysed in blood samples at 2 and 5 days post-stroke, and brain miRNAs were analysed at 5 days post-stroke. Although stroke-associated infarction was observed in all groups, infarct volume and sensory-motor deficits were significantly reduced in adult females compared with middle-aged females, adult males or middle-aged males. At 2 days post-stroke, 21 circulating miRNAs were differentially regulated and PCA (principal component analysis) confirmed that most of the variance was due to age. At 5 days post-stroke, 78 circulating miRNAs exhibited significantly different regulation, and most of the variance was associated with sex. A small cohort (five) of miRNAs, miR-15a, miR-19b, miR-32 miR-136 and miR-199a-3p, were found to be highly expressed exclusively in adult females compared with middle-aged females, adult males and middle-aged males. Predicted gene targets for these five miRNAs analysed for KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed that the top ten KEGG pathways were related to growth factor signalling, cell structure and PI3K (phosphoinositide 3-kinase)/Akt and mTOR (mammalian target of rapamycin) signalling. Overall, the pattern of circulating miRNA expression suggests an early influence of age in stroke pathology, with a later emergence of sex as a factor for stroke severity.
循环中小非编码 RNA（miRNA（微 RNA））已成功用作慢性和急性疾病的生物标志物和机制靶点。本研究在动物模型中研究了年龄和性别对缺血性中风后 miRNA 表达的影响。成年（6 个月）和中年（11-12 个月）雌性和雄性大鼠通过 ET-1（内皮素-1）接受 MCAo（大脑中动脉闭塞）。在中风后 2 和 5 天分析血液样本中的循环 miRNA，并在中风后 5 天分析大脑 miRNA。尽管所有组都观察到与中风相关的梗死，但与中年雌性、成年雄性或中年雄性相比，成年雌性的梗死体积和感觉运动缺陷明显减少。中风后 2 天，21 个循环 miRNA 差异调节，PCA（主成分分析）证实大多数差异归因于年龄。中风后 5 天，78 个循环 miRNA 表现出明显不同的调节，大部分差异与性别有关。一小部分（五个）miRNA，miR-15a、miR-19b、miR-32、miR-136 和 miR-199a-3p，仅在成年雌性中高度表达，而在中年雌性、成年雄性和中年雄性中则未发现。对这五个 miRNA 的预测基因靶标进行了 KEGG（京都基因与基因组百科全书）通路分析，结果表明前 10 个 KEGG 通路与生长因子信号、细胞结构以及 PI3K（磷酸肌醇 3-激酶）/Akt 和 mTOR（雷帕霉素哺乳动物靶标）信号有关。总的来说，循环 miRNA 表达模式表明年龄对中风病理的早期影响，随后性别成为中风严重程度的一个因素。
