Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Int J Mol Med. 2021 May;47(5). doi: 10.3892/ijmm.2021.4923. Epub 2021 Mar 31.
Abdominal aortic aneurysm (AAA) is a pathological state with permanent dilation, which indicates a fatal potential for aortic rupture. It has been reported that dexmedetomidine (Dex) and microRNA (miR)‑21 are involved in the progression of AAA. Thus, the present study aimed to investigate the joint effects of these factors on AAA treatment. For this purpose, rat models of AAA were established with enzyme perfusion and the rats were then injected with Dex. Alterations in the abdominal aorta in rats with AAA were recorded. miR‑21 expression in the rats with AAA was determined. Inflammatory factor expression was detected by western blot analysis. Subsequently, a dual‑luciferase reporter gene assay was performed to verify the targeting association between miR‑21 and programmed cell death protein 4 (PDCD4). Additionally, AAA‑related indices and inflammatory responses were examined by an injection of a combination of antagomiR (ant)‑miR‑21 and Dex or lentivirus‑PDCD4‑short hairpin RNA. It was found that Dex markedly alleviated the development of AAA and downregulated the expression of inflammatory factors and matrix metalloproteinase in rats with AAA. The high expression of miR‑21, which targets PDCD4, was observed in the rats with AAA. However, ant‑miR‑21 induced AAA development and inflammatory responses. Additionally, the inhibition of PDCD4 reduced AAA development and inflammatory responses. On the whole, the present study demonstrates that Dex inhibits AAA development by downregulating the miR‑21/PCDP4 axis. The findings of the present study may provide novel insight for the treatment of AAA. These findings may provide a reference for the future treatment of AAA and may provide theoretical guidance for the early prevention and development of AAA.
腹主动脉瘤(AAA)是一种永久性扩张的病理性状态,表明主动脉破裂具有致命的潜在风险。据报道,右美托咪定(Dex)和 microRNA(miR)-21 参与 AAA 的进展。因此,本研究旨在探讨这些因素对 AAA 治疗的联合作用。为此,采用酶灌注建立大鼠 AAA 模型,然后给大鼠注射 Dex。记录大鼠 AAA 腹主动脉的变化。检测大鼠 AAA 中 miR-21 的表达。通过 Western blot 分析检测炎症因子的表达。随后,进行双荧光素酶报告基因检测以验证 miR-21 与程序性细胞死亡蛋白 4(PDCD4)之间的靶向关联。此外,通过注射抗 miR-21 和 Dex 或慢病毒-PDCD4-短发夹 RNA 组合来检查与 AAA 相关的指数和炎症反应。结果发现,Dex 显著缓解 AAA 的发展,并下调 AAA 大鼠炎症因子和基质金属蛋白酶的表达。在 AAA 大鼠中观察到 miR-21 的高表达,其靶向 PDCD4。然而,抗 miR-21 诱导 AAA 发展和炎症反应。此外,PDCD4 的抑制减少了 AAA 的发展和炎症反应。总的来说,本研究表明 Dex 通过下调 miR-21/PCDP4 轴抑制 AAA 的发展。本研究的结果可为 AAA 的治疗提供新的见解。这些发现可为 AAA 的未来治疗提供参考,并为 AAA 的早期预防和发展提供理论指导。