α细辛醚开启斑马鱼血脑屏障作用机制和其生物安全性的研究.pdfVIP

作用2h又逐渐的恢复，到8h基本恢复正常水平。将斑马鱼胚胎暴露在不同浓度 的旺．细辛醚溶液中，24hpf斑马鱼自主抽动的次数降低；48hpf斑马鱼的心率减 低；72hpf斑马鱼幼鱼有脊柱弯曲、心包水肿、尾巴弯曲、卵黄囊水肿等畸形的 表征；96hpf斑马鱼幼鱼的孵化率、死亡率有很大的差异；通过斑马鱼幼鱼运动 行为学表明随着0【．细辛醚浓度增加，斑马鱼幼鱼运动受到抑制。 本文的结论为芳香开窍药能使紧密连接蛋白claudin家族基因表达下调，致 使紧密连接结构疏松，加之基膜结构破坏，内皮细胞皱缩，使得血脑屏障的屏障 作用减弱，从而开启了血脑屏障，发挥了开窍的作用。基因可逆性的下调说明C【． 细辛醚对血脑屏障是生理性的，对脑部不会带来病理学损伤。从用药安全性来看， 高浓度的0【．细辛醚对斑马鱼胚胎发育有明显毒性作用。提示人畜临床慎用仅．细 辛醚。 关键词：C【．细辛醚；血脑屏障；开窍机制；Claudin家族；毒性 万方数据 Cc．asarone Blood-Brain of ontheMechanism Regulation Studv Barrierand inZebrafish SafeW Biological Abstract barrier onzebrafishbrain of 0【．asarone tight theinfluence Tostudv drugs andthe of family iunctionstructure geneprotein expression brainbarrier· theblood mechanismofa-asarone orderto the open JAM．In study evaluationthe and While ofthezebrafish developmentreproductlVe advantage taking C【一asaroneon of embuonic． toxicity substance fluorescent Heart to macromolecular Methods help taking injection by after 0【一asarone to uvenilezebrafishadministrating Redected DextranTexas inj j substance fluorescent C【．asaronecan macromolecular observed solution． help oI electron toobservestructure ofblood—brain microscrope 1 ermeability barrier．By brain ofthezebrafish ontheultrastructure after旺一asarone barrieraffects blood-brain observed real—time tissueslices structure；usmg zebrafishbrain barrier．affecting 0【一asarone PCR Real．time inzebrafish auantitative quantitativejRT-qPCR studies affect expressmn· closel、，connectedClaudinj ZOjoccludin，JAMgene family zebrafish 3 embr370S s。lutiontake O【．asarone hpf Hourspost—ferilization，hpf at morphological concentrations exDosedtodif免rent 24hpf．48hpf．72hpf,96hpf statistical of embryosindependent obserration development．zebrafish embryonic rateand rate．heart deformitymortalit?7 rate：embry sDontaneousmovements．hatching sac edema as phenomenon；the andother yolk edema：pericardial morphol093，．such PCR at withreal—time tecbmique exDressionof l wasdetermined quantitatix7e sepn NoldustOevaluatethe of behavioral impact Theuseofzebrafi