Park Je Hoon, Ko Il Gyu, Kim Sung Eun, Jin Jun Jang, Hwang Lakkyong, Kim Chang Ju, Yoon Soo Hwan, Hong Jongki, Chung Jun Young, Lee Deok Won
Department of Surgery, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon, Korea.
Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
Int Neurourol J. 2017 Apr;21(Suppl 1):S39-47. doi: 10.5213/inj.1734884.442. Epub 2017 Apr 21.
Dexmedetomidine, an α2-adrenergic agonist, provides sedative and analgesic effects without significant respiratory depression. Dexmedetomidine has been suggested to have an antiapoptotic effect in response to various brain insults. We developed an oral mucosa patch using dexmedetomidine for sedation. The effects of the dexmedetomidine oral mucosa patch on cell proliferation and apoptosis in the hippocampus were evaluated.
A hydrogel oral mucosa patch was adhered onto the oral cavity of physiologically normal rats, and was attached for 2 hours, 6 hours, 12 hours, or 24 hours. Plasma dexmedetomidine concentrations were determined by liquid chromatography- electrospray ionization-tandem mass spectrometry-multiple-ion reaction monitoring (LC-ESI-MS/MS-MRM). Cell proliferation in the hippocampus was detected by Ki-67 immunohistochemistry. Caspase-3 immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and Western blotting for Bax and Bcl-2 were performed to detect hippocampal apoptosis. The levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) in the hippocampus were also measured by Western blotting.
Plasma dexmedetomidine concentration increased according to the attachment time of the dexmedetomidine oral mucosa patch. Hippocampal cell proliferation did not change due to the dexmedetomidine oral mucosa patch, and the dexmedetomidine oral mucosa patch exerted no significant effect on BDNF or TrkB expression. In contrast, the dexmedetomidine oral mucosa patch exerted an antiapoptotic effect depending on the attachment time of the dexmedetomidine oral mucosa patch.
A dexmedetomidine oral mucosa patch can be used as a convenient tool for sedation, and is of therapeutic value due to its antiapoptotic effects under normal conditions.
右美托咪定是一种α2肾上腺素能激动剂，具有镇静和镇痛作用，且无明显呼吸抑制。右美托咪定已被认为在应对各种脑损伤时具有抗凋亡作用。我们研发了一种使用右美托咪定的口腔黏膜贴片用于镇静。评估了右美托咪定口腔黏膜贴片对海马体中细胞增殖和凋亡的影响。
将水凝胶口腔黏膜贴片贴于生理正常大鼠的口腔，分别贴2小时、6小时、12小时或24小时。通过液相色谱 - 电喷雾电离 - 串联质谱 - 多离子反应监测（LC - ESI - MS/MS - MRM）测定血浆右美托咪定浓度。通过Ki - 67免疫组织化学检测海马体中的细胞增殖。进行Caspase - 3免疫组织化学、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色以及Bax和Bcl - 2的蛋白质印迹法以检测海马体凋亡。还通过蛋白质印迹法测量海马体中脑源性神经营养因子（BDNF）和酪氨酸激酶B（TrkB）的水平。
血浆右美托咪定浓度随右美托咪定口腔黏膜贴片的贴附时间增加。右美托咪定口腔黏膜贴片未导致海马体细胞增殖发生变化，且对BDNF或TrkB表达无显著影响。相比之下，右美托咪定口腔黏膜贴片根据其贴附时间发挥抗凋亡作用。
右美托咪定口腔黏膜贴片可作为一种方便的镇静工具，并且由于其在正常条件下的抗凋亡作用而具有治疗价值。
