Dexmedetomidine protects gastric mucosal epithelial cells against ischemia/reperfusion-induced apoptosis by inhibiting HMGB1-mediated inflammation and oxidative stress

作者全名："Liu, Tianpin; Wang, Bing; Han, Qiong; Gong, Wansheng; Ye, Juan"

作者地址："[Liu, Tianpin] China Three Gorges Univ, Coll Clin Med Sci 1, Dept Anesthesiol, Yichang 443003, Hubei, Peoples R China; [Liu, Tianpin] Yichang Cent Peoples Hosp, Dept Anesthesiol, Yichang 443003, Hubei, Peoples R China; [Wang, Bing; Han, Qiong; Gong, Wansheng] Yichang Zigui Cty Peoples Hosp, Dept Anesthesiol, Yichang 443600, Hubei, Peoples R China; [Ye, Juan] Chongqing Med Univ, Banan Hosp, Dept Anesthesiol, Chongqing 401320, Peoples R China"

通信作者："Ye, J (通讯作者)，Chongqing Med Univ, Banan Hosp, Dept Anesthesiol, Chongqing 401320, Peoples R China."

来源：TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000859868900008

JCR分区：Q4

影响因子：0.6

年份：2022

卷号：21

期号：7

开始页：1411

结束页：1417

文献类型：Article

关键词：Dexmedetomidine; gastric mucosal epithelial cells; Ischemia/reperfusion; Apoptosis; Inflammation; Oxidative stress; High-mobility group box 1 (HMGB1)

摘要："Purpose: To investigate the role of dexmedetomidine in gastric ischemia/reperfusion injury using gastric mucosal epithelial cell (GES-1) model. Methods: GES-1 were subjected to oxygen-glucose deprivation conditions, followed by increasing dexmedetomidine concentrations (0.5, 1.0, or 1.5 NM) for 4 h of reoxygenation. Cell viability and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide and flow cytometry, respectively. Oxidative stress and inflammation were analyzed by enzyme-linked immunosorbent assay (ELISA). Results: Oxygen-glucose deprivation conditions induced cytotoxicity in GES-1 by decreasing cell viability and increasing apoptosis. Dexmedetomidine treatment significantly increased the cell viability of hypoxia/reoxygenation-induced GES-1 (p < 0.01) but reduced apoptosis. Dexmedetomidine also attenuated the hypoxia/reoxygenation-induced increase in malondialdehyde and myeloperoxidase, but the decrease in superoxide dismutase and glutathione in GES-1. Moreover, upregulated tumor necrosis factor-alpha, interleukin IL-1 beta, and IL-18 in hypoxia/reoxygenation-induced GES-1 was downregulated by dexmedetomidine treatment. Dexmedetomidine also enhanced IL-10 levels and inhibited proinflammatory factor production (p < 0.01). High-mobility group box 1 (HMGB1) protein in GES-1 was upregulated by hypoxia/reoxygenation but decreased by dexmedetomidine. HMGB1 over-expression attenuated the dexmedetomidine-induced increase in cell viability and the decrease in apoptosis, oxidative stress, and inflammation in hypoxia/reoxygenation-induced GES-1 (p < 0.01). Conclusion: Dexmedetomidine protects GES-1 against ischemia/reperfusion-induced apoptosis, inflammation, and oxidative stress by inhibiting HMGB1, thus providing a potential strategy for treating gastric ischemia/reperfusion injury."

基金机构：Yichang Medical and Health Research Project [A22-2-013]

基金资助正文：This work was supported by Yichang Medical and Health Research Project in 2022 (Grant no. A22-2-013).