Recent studies have shown that long non-coding RNA(LncRNA) H19 is up-regulated in the brain of rats suffering from cerebral ischemia-reperfusion (I/R) injury, inducing severe disability and mortality. Little was known about the molecular mechanisms underlying the involvement of H19 in cerebral I/R injury. In this study, a rat model of I/R was induced by transient middle cerebral artery occlusion (tMCAO). PC-12 cells exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) were used as an in vitro model. Our results show that H19 is up-regulated in both in vivo and in our in vitro model. Further study indicated that knockdown of H19 promotes cell proliferation, decreases the rate of cell apoptosis, and ameliorates inflammation after OGD/R simulation. Our in vivo study shows that H19 knockdown ameliorates inflammation and improves neurological function in our rat model of tMCAO. Remarkably, the results from our luciferase reporter assays suggest that H19 negatively regulates the expression of miR-138-5p, and p65 was identified as a target of miR-138-5p. To sum up, this study demonstrated that H19 promotes an inflammatory response and improves neurological function in a rat model of tMCAO by regulating the expression of miR-138-5p and p65. This study reveals the important role and underlying mechanism of H19 in the progress of cerebral I/R injury, which could serve as a potential target for further treatment.

中文翻译：

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LncRNA H19通过调节miR-138-5p-p65轴促进由脑缺血再灌注损伤诱导的炎症反应。

最近的研究表明，长时非编码RNA（LncRNA）H19在遭受脑缺血再灌注（I / R）损伤的大鼠的大脑中上调，从而导致严重的残疾和死亡。关于H19参与脑I / R损伤的分子机制知之甚少。在这项研究中，通过短暂性中脑动脉闭塞（tMCAO）诱导了I / R大鼠模型。暴露于氧气和葡萄糖剥夺/复氧（OGD / R）的PC-12细胞用作体外模型。我们的结果表明，H19在体内和体外模型中均上调。进一步的研究表明，在OGD / R模拟后，敲除H19可以促进细胞增殖，降低细胞凋亡率，并改善炎症。我们的体内研究表明，在我们的tMCAO大鼠模型中，H19敲低可减轻炎症并改善神经功能。值得注意的是，我们萤光素酶报告基因检测的结果表明，H19负调控miR-138-5p的表达，而p65被确定为miR-138-5p的靶标。综上所述，该研究证明H19通过调节miR-138-5p和p65的表达促进tMCAO大鼠模型的炎症反应并改善其神经功能。这项研究揭示了H19在脑I / R损伤进展中的重要作用及其潜在机制，可以作为进一步治疗的潜在靶标。p65被确定为miR-138-5p的靶标。综上所述，该研究表明，H19通过调节miR-138-5p和p65的表达促进tMCAO大鼠模型的炎症反应并改善其神经功能。这项研究揭示了H19在脑I / R损伤进展中的重要作用及其潜在机制，可以作为进一步治疗的潜在靶标。p65被确定为miR-138-5p的靶标。综上所述，该研究表明，H19通过调节miR-138-5p和p65的表达促进tMCAO大鼠模型的炎症反应并改善其神经功能。这项研究揭示了H19在脑I / R损伤进展中的重要作用及其潜在机制，可以作为进一步治疗的潜在靶标。