Zhao Shankun, Wu Weizhou, Lin Xuezheng, Shen Maolei, Yang Zhenyu, Yu Sicong, Luo Yu
Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, Zhejiang, China.
Department of Urology, Maoming People's Hospital, Maoming, 525000, Guangdong, China.
Cell Mol Biol Lett. 2022 May 4;27(1):34. doi: 10.1186/s11658-022-00335-7.
Vital organ injury is one of the leading causes of global deaths. Accumulating studies have demonstrated that dexmedetomidine (DEX) has an outstanding protective effect on multiple organs for its antiinflammatory and antiapoptotic properties, while the underlying molecular mechanism is not clearly understood. Autophagy, an adaptive catabolic process, has been found to play a crucial role in the organ-protective effects of DEX. Herein, we present a first attempt to summarize all the evidence on the proposed roles of autophagy in the action of DEX protecting against vital organ injuries via a comprehensive review. We found that most of the relevant studies (17/24, 71%) demonstrated that the modulation of autophagy was inhibited under the treatment of DEX on vital organ injuries (e.g. brain, heart, kidney, and lung), but several studies suggested that the level of autophagy was dramatically increased after administration of DEX. Albeit not fully elucidated, the underlying mechanisms governing the roles of autophagy involve the antiapoptotic properties, inhibiting inflammatory response, removing damaged mitochondria, and reducing oxidative stress, which might be facilitated by the interaction with multiple associated genes (i.e., hypoxia inducible factor-1α, p62, caspase-3, heat shock 70 kDa protein, and microRNAs) and signaling cascades (i.e., mammalian target of rapamycin, nuclear factor-kappa B, and c-Jun N-terminal kinases pathway). The authors conclude that DEX hints at a promising strategy in the management of vital organ injuries, while autophagy is crucially involved in the protective effect of DEX.
重要器官损伤是全球死亡的主要原因之一。越来越多的研究表明，右美托咪定（DEX）因其抗炎和抗凋亡特性，对多个器官具有显著的保护作用，但其潜在的分子机制尚不清楚。自噬是一种适应性分解代谢过程，已发现其在DEX的器官保护作用中起关键作用。在此，我们首次尝试通过全面综述，总结关于自噬在DEX预防重要器官损伤作用中所提出作用的所有证据。我们发现，大多数相关研究（17/24，71%）表明，在DEX治疗重要器官损伤（如脑、心、肾和肺）时，自噬的调节受到抑制，但有几项研究表明，给予DEX后自噬水平显著升高。尽管尚未完全阐明，但自噬作用的潜在机制涉及抗凋亡特性、抑制炎症反应、清除受损线粒体和减轻氧化应激，这可能通过与多个相关基因（即缺氧诱导因子-1α、p62、半胱天冬酶-3、热休克70 kDa蛋白和微小RNA）以及信号级联反应（即雷帕霉素靶蛋白哺乳动物、核因子-κB和c-Jun氨基末端激酶途径）的相互作用而得到促进。作者得出结论，DEX为重要器官损伤的管理提供了一种有前景的策略，而自噬在DEX的保护作用中至关重要。
