Overexposure to 1,2-dichloroethane (1,2-DCE) can induce brain edema, but the underlying mechanisms remain largely unknown. Aquaporin 4 (AQP4) is the most prevalent water channel in the brain, and the pool of AQP4 facilitates brain edema by controlling the inflow and clearance of brain water. MicroRNAs play an important role in the regulation of brain edema via RNA silencing and post-transcriptional regulation of gene expression. To explore the regulation role of AQP4 and microRNA in 1,2-DCE-induced brain edema, Sprague-Dawley (SD) rats and AQP4 knockout CD-1 mice were exposed to 1,2-DCE by inhalation for 7 days (0, 600, 1800 mg/m3) and 28 days (0, 100, 350, 700 mg/m3), respectively. The results showed that 1,2-DCE induces brain edema, in both rats and mice, characterized by an increase in brain water content and vacuolations in the brain parenchyma and around the vessels of the cerebral cortex. Notably, 1,2-DCE exposure can down-regulate AQP4 expression, in both rats and mice. Also, deleting AQP4 intensifies 1,2-DCE-induced brain edema in mice. Meanwhile, microRNA-29b-3p (miR-29b) expression increases with 1,2-DCE exposure, in both rats and mice. A negative correlation was found between the expression of miR-29b and AQP4 in vivo. Moreover, the negative regulation of miR-29b by direct targeting to AQP4 was confirmed by dual luciferase reporter assay in vitro. Taken together, our findings indicate that AQP4 plays an important role in balancing water content in 1,2-DCE-induced brain edema. The dysregulation of miR-29b after 1,2-DCE exposure can aggravate brain edema by directly suppressing the expression of AQP4.

中文翻译：

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MicroRNA-29b-3p 通过靶向 Sprague-Dawley 大鼠和 CD-1 小鼠的水通道蛋白 4 加重 1,2-二氯乙烷诱导的脑水肿

过度暴露于 1,2-二氯乙烷 (1,2-DCE) 会导致脑水肿，但其潜在机制在很大程度上仍然未知。水通道蛋白 4 (AQP4) 是大脑中最普遍的水通道，AQP4 池通过控制脑水的流入和清除来促进脑水肿。MicroRNA 通过 RNA 沉默和基因表达的转录后调控在脑水肿的调控中发挥重要作用。为了探讨 AQP4 和 microRNA 在 1,2-DCE 诱导的脑水肿中的调节作用，Sprague-Dawley (SD) 大鼠和 AQP4 敲除 CD-1 小鼠通过吸入暴露于 1,2-DCE 7 天（0, 600、1800 毫克/立方米）和 28 天（0、100、350、700 毫克/立方米）。结果表明 1,2-DCE 在大鼠和小鼠中均诱导脑水肿，其特征是脑实质和大脑皮层血管周围脑水含量增加和空泡化。值得注意的是，1,2-DCE 暴露可以下调大鼠和小鼠的 AQP4 表达。此外，删除 AQP4 会加剧 1,2-DCE 诱导的小鼠脑水肿。同时，在大鼠和小鼠中，microRNA-29b-3p (miR-29b) 表达随着 1,2-DCE 暴露而增加。在体内 miR-29b 和 AQP4 的表达之间发现负相关。此外，通过体外双荧光素酶报告基因测定证实了直接靶向 AQP4 对 miR-29b 的负调节。总之，我们的研究结果表明 AQP4 在平衡 1,2-DCE 诱导的脑水肿中的水含量方面起着重要作用。1 后 miR-29b 的失调，