Brain research bulletin · 2025
Dexmedetomidine attenuates postoperative delirium by activating Nrf2 to reduce oxidative stress and blood-brain barrier disruption.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Feng Tengchen, Yao Jie, Chen Yanlin, Wang Jiayi, Zhu Ying, Lan Zhiming, Huo Xuhua, Wang Yeming, Gao Jingui
Аннотация
BACKGROUND: Postoperative delirium (POD), characterized by cognitive dysfunction, is a prevalent and severe complication following surgery. The blood-brain barrier (BBB) is crucial in maintaining central nervous system (CNS) homeostasis, and its disruption is associated with POD. Dexmedetomidine (DEX), an α2-adrenergic receptor agonist, potentially reduces POD incidence by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which regulates antioxidant responses and alleviates BBB damage.
METHODS: This study used transcriptomic analysis to identify differentially expressed genes in patients with POD and explored the therapeutic targets of DEX. In vitro experiments using HCMEC/D3 cells and an in vivo mouse model of POD were conducted to assess the effects of DEX on BBB integrity and neuroinflammation. Western blotting, flow cytometry, and ELISA were used to evaluate protein expression, apoptosis, and cytokine levels, respectively. Behavioral tests (open-field and Y-maze tests) were performed to assess cognitive function in mice.
RESULTS: Bioinformatics analysis revealed Nrf2 as a key target of DEX. DEX treatment significantly increased Nrf2 expression and alleviated oxidative stress and neuroinflammation in HCMEC/D3 cells. In the POD mouse model, DEX improved cognitive function, evidenced by enhanced performance in behavioral tests. DEX also upregulated Nrf2 expression in the mouse brain tissue and reduced serum inflammatory. Furthermore, DEX preserved BBB integrity by upregulating tight junction proteins, which was reversed by the Nrf2 inhibitor, ML385.
CONCLUSIONS: DEX ameliorates POD by activating Nrf2, thereby reducing oxidative stress and inflammation, and maintaining BBB integrity. These findings suggest DEX is a potential therapeutic agent for POD, highlighting the Nrf2 pathway as a novel target for treatment strategies.
METHODS: This study used transcriptomic analysis to identify differentially expressed genes in patients with POD and explored the therapeutic targets of DEX. In vitro experiments using HCMEC/D3 cells and an in vivo mouse model of POD were conducted to assess the effects of DEX on BBB integrity and neuroinflammation. Western blotting, flow cytometry, and ELISA were used to evaluate protein expression, apoptosis, and cytokine levels, respectively. Behavioral tests (open-field and Y-maze tests) were performed to assess cognitive function in mice.
RESULTS: Bioinformatics analysis revealed Nrf2 as a key target of DEX. DEX treatment significantly increased Nrf2 expression and alleviated oxidative stress and neuroinflammation in HCMEC/D3 cells. In the POD mouse model, DEX improved cognitive function, evidenced by enhanced performance in behavioral tests. DEX also upregulated Nrf2 expression in the mouse brain tissue and reduced serum inflammatory. Furthermore, DEX preserved BBB integrity by upregulating tight junction proteins, which was reversed by the Nrf2 inhibitor, ML385.
CONCLUSIONS: DEX ameliorates POD by activating Nrf2, thereby reducing oxidative stress and inflammation, and maintaining BBB integrity. These findings suggest DEX is a potential therapeutic agent for POD, highlighting the Nrf2 pathway as a novel target for treatment strategies.