The functional roles of microRNAs (miRNAs) have been studied in various diseases, including hypoxic-ischemic brain damage (HIBD). However, changes in the expression of miRNAs and the underlying mechanisms in the pineal gland during HIBD remain unknown. Based on the previous study by microRNA array, hundreds of miRNAs showed altered expression patterns in the pineal gland in a rat model of HIBD. MiR-375-3p was found to be significantly upregulated and abundant in the pineal gland. Further investigation in an in vitro HI model of pinealocytes showed that miRNA-375 exacerbated the damage to pineal function. After oxygen-glucose deprivation / reoxygenation (OGD/R), miR-375-3p expression increased, while aralkylamine N-acetyltransferase (AANAT) expression and melatonin (MT) secretion decreased. Overexpression of miRNA-375 in pinealocytes aggravated the influence of OGD/R on AANAT expression and MT secretion. Because miRNA-375 overexpression in pinealocytes induced decreased rasd1 mRNA and protein expression, rasd1 may mediate the effect of miR-375-3p on pineal function. Furthermore, miR-375-3p aggravated the cognitive impairment caused by HIBD in rats, as observed by Morris water maze test, and also affected emotion and circadian rhythm in HIBD-treated rats. Thus, miR-375-3p may be a key regulatory molecule in the pineal gland following HIBD, and targeting of miR-375-3p may represent a new strategy for the treatment of HIBD.

已经研究了微 RNA (miRNA) 在各种疾病中的功能作用，包括缺氧缺血性脑损伤 (HIBD)。然而，在 HIBD 期间 miRNA 表达的变化和松果体中的潜在机制仍然未知。基于之前通过 microRNA 阵列进行的研究，数百种 miRNA 在 HIBD 大鼠模型的松果体中显示出改变的表达模式。发现 MiR-375-3p 在松果体中显着上调且含量丰富。在松果体细胞的体外 HI 模型中的进一步研究表明 miRNA-375 加剧了对松果体功能的损害。氧-葡萄糖剥夺/复氧 (OGD/R) 后，miR-375-3p 表达增加，而芳烷基胺N-乙酰转移酶 (AANAT) 表达和褪黑激素 (MT) 分泌减少。松果体细胞中miRNA-375的过表达加重了OGD/R对AANAT表达和MT分泌的影响。由于松果体细胞中 miRNA-375 过表达导致 rasd1 mRNA 和蛋白质表达降低，rasd1 可能介导 miR-375-3p 对松果体功能的影响。此外，如Morris水迷宫试验所观察到的，miR-375-3p加重了HIBD引起的大鼠认知障碍，并且还影响了HIBD治疗大鼠的情绪和昼夜节律。因此，miR-375-3p 可能是 HIBD 后松果体中的关键调节分子，靶向 miR-375-3p 可能代表了治疗 HIBD 的新策略。