上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2020, Vol. 40 ›› Issue (2): 157-.doi: 10.3969/j.issn.1674-8115.2020.02.003

• 论著·基础研究 • 上一篇    下一篇

格列本脲经鼻给药对小鼠创伤性脑损伤的治疗作用

王 矩1，陈 瑾2，徐馨璐2，余 琪2，宋明柯1   

  1. 1. 上海交通大学基础医学院药理学与化学生物学系，上海 200025；2. 上海交通大学医学院2015级临床医学八年制二大班，上海 200025
  • 出版日期:2020-02-28 发布日期:2020-03-20
  • 通讯作者: 宋明柯，电子信箱：mksong@sjtu.edu.cn。
  • 作者简介:王 矩（1995—），女，硕士生；电子信箱：wangju5201@126.com。
  • 基金资助:
    国家自然科学基金（91949116，81873807）；2018-2019上海市高水平地方高校建设项目（XD18012）；上海交通大学医学院RBL项目（2017-2018）。

Effect of intranasal administration of glibenclamide on the treatment of traumatic brain injury in mice

WANG Ju, CHEN Jin, XU Xin-Lu, YU Qi, SONG Ming-ke   

  1. 1. Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China; 2. Class 2 of Grade 2015, Clinical Medicine Eight-Year Program, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2020-02-28 Published:2020-03-20
  • Supported by:
    National Natural Science Foundation of China (91949116, 81873807); 2018-2019 Shanghai High-level College Construction Project (XD18012); Research-Based Learning Project of Shanghai Jiao Tong University School of Medicine (2017-2018).

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摘要： 目的·观察格列本脲经鼻给药对创伤性脑损伤（traumatic brain injury，TBI）的治疗作用，为TBI的药物治疗提供新思路。方法·8周龄C57BL/6J小鼠随机分为格列苯脲治疗组（n21）、对照组（n19）和活体荧光成像组（n1）。活体荧光成像组小鼠经鼻注入荧光探针标记的格列苯脲，观察药物的入脑情况。采用控制性皮层撞击法于上述前2组小鼠右脑半球建立TBI模型。格列苯脲治疗组小鼠在TBI造模成功后经鼻注入格列苯脲，对照组小鼠则经鼻注入等剂量的药物溶剂。于TBI造模成功24 h后处死小鼠，采用干湿比重法测定2组小鼠脑水肿的程度，采用2, 3, 5-三苯基氯化四氮唑染色法测量该2组小鼠脑组织损伤体积，并通过转棒实验评价其神经功能变化。结果·活体荧光成像实验显示格列苯脲经鼻给药后成功到达脑部。对照组小鼠脑水肿程度和损伤体积明显大于格列苯脲治疗组（均P结论·格列苯脲经鼻给药能显著减轻TBI诱发的脑水肿、减少脑损伤体积，提示该药物对TBI具有一定的神经保护作用。

关键词: 创伤性脑损伤, 格列本脲, 脑水肿, 经鼻给药

Abstract:

Objective · To observe the effect of intranasal administration of glibenclamide on the treatment of traumatic brain injury (TBI), providing new ideas for the treatment of TBI. Methods · Eight-week-old C57BL/6J mice were randomly divided into glibenclamide treatment group (n21), control group (n19) and in vivo fluorescence imaging group (n1). Glibenclamide labeled with fluorescent probe was injected into the nose of mice in the in vivo fluorescence imaging group to observe the transportation of glibenclamide into the brain. The TBI model was established in the right hemisphere of mobrain of the glibenclamide treatment group and the control groupthe controlled cortical impact (CCI) method. The mice in the glibenclamide treatment group received intranasal delivery of the drug after TBI induction, while the mice in the control group received equal doses of the solvent without glibenclamide under the same conditions. Mice were decapitated after 24 h of successful modeling. The degree of brain edema in the two groups was measuredthe percentage change in water content of brain tissues. The volume of brain damage in the two groups was measured2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The neurological function of the two groups was evaluatedrotarod test. Results · In vivo fluorescence imaging experiment showed that glibenclamide successfully reached the brain after intranasal administration. The degree of brain edema and the volume of brain damage in the control group were significantly larger than those in the glibenclamide treatment group (both PConclusion · Intranasal delivery of glibenclamide can significantly reduce TBI-caused brain edema and brain damage volume, suggesting that the drug has a certain neuroprotective effect on TBI.

Key words: traumatic brain injury (TBI), glibenclamide, brain edema, intranasal administration