Objective

Hypoxic-ischemic brain damage (HIBD) is a common brain injury caused by hypoxia or ischemia of the brain. This study aims to investigate the effect of dexmedetomidine (Dex) post-treatment on neurological impairment of newborn rats with HIBD via modulating microRNA-29a-3p (miR-29a-3p) and histone deacetylase 4 (HDAC4).

Methods

HIBD model of newborn rats was established. Newborn modeled rats were injected with Dex, miR-29a-3p mimic or HDAC4 siRNA to figure their roles in learning and memory abilities, left hemisphere atrophy, brain tissue injury, inflammatory response and apoptosis rate of nerve cells of rats. The expression of miR-29a-3p and HDAC4 in hippocampal tissues of rats were detected, and the potential relationship between miR-29a-3p and HDAC4 was analyzed.

Results

Decreased miR-29a-3p and elevated HDAC4 were found in hippocampal tissues of rats with HIBD. In addition, Dex, elevated miR-29a-3p or declined HDAC4 enhanced spatial learning and memory abilities in rats with HIBD. Moreover, Dex, up-regulated miR-29a-3p or declined HDAC4 alleviated brain atrophy, repressed brain tissue injury, retrained the inflammation, repressed the apoptosis of neurons in the hippocampal region of rats with HIBD. HDAC4 was targeted and negatively regulated by miR-29a-3p.

Conclusion

The study concludes that miR-29a-3p strengthened the effect of Dex on improving neurologic damage in newborn rats with HIBD by inhibiting HDAC4.

中文翻译：

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MicroRNA-29a-3p通过抑制HDAC4增强右美托咪定改善缺氧缺血性脑损伤新生大鼠神经损伤的作用

 客观的

缺氧缺血性脑损伤（ HIBD）是由大脑缺氧或缺血引起的常见脑损伤。本研究旨在探讨右美托咪定 (Dex) 治疗后通过调节 microRNA-29a-3p (miR-29a-3p) 和组蛋白脱乙酰酶 4 (HDAC4) 对 HIBD 新生大鼠神经功能损伤的影响。

 方法

建立新生大鼠HIBD模型。给新生模型大鼠注射Dex、miR-29a-3p模拟物或HDAC4 siRNA，观察它们对大鼠学习记忆能力、左半球萎缩、脑组织损伤、炎症反应和神经细胞凋亡率的作用。检测大鼠海马组织中miR-29a-3p和HDAC4的表达情况，分析miR-29a-3p与HDAC4之间的潜在关系。

 结果

在 HIBD 大鼠的海马组织中发现 miR-29a-3p 减少和 HDAC4 升高。此外，Dex、升高的 miR-29a-3p 或降低的 HDAC4 增强了 HIBD 大鼠的空间学习和记忆能力。此外，Dex、上调miR-29a-3p或降低HDAC4可减轻HIBD大鼠的脑萎缩、抑制脑组织损伤、重新训练炎症、抑制海马区神经元凋亡。 HDAC4 受到 miR-29a-3p 的靶向和负调控。

 结论

研究结论是，miR-29a-3p 通过抑制 HDAC4 增强了 Dex 改善 HIBD 新生大鼠神经损伤的作用。