In?vitro analysis of drugs that improve hyperglycemia-induced blood-brain barrier dysfunction 高血糖により惹起される血液脳関門機能障害を改善する薬剤に関する in vitro分析

Background: Blood-brain barrier (BBB) disruptions are a key feature of hyperglycemia (HG)-induced cerebral damage. Patients with diabetes mellitus often have other cerebrovascular disease risk factors including hypertension, dyslipidemia, arrhythmia, and atherosclerosis obliterans. However, whether the drugs for these comorbidities are effective for improving HG-induced BBB damage is unclear. Methods: We investigated the effect of pitavastatin, candesartan, cilostazol, propranolol, and eicosapentaenoic acid on HG-induced BBB damage. In vitro BBB models consisting of primary cultures of rat brain capillary endothelial cells were subjected to HG (55?mM d-glucose). Results: We observed a significant decrease in transendothelial electrical resistance (TEER) with HG, showing that HG compromised the integrity of the in vitro BBB model. No significant decrease in cell viability was seen with HG, but HG increased the production of reactive oxygen species. Pitavastatin and candesartan inhibited decreases in TEER induced by HG. Conclusions: In summary, pitavastatin and candesartan improved HG-induced BBB damage and this in vitro model of HG-induced BBB dysfunction contributes to the search for BBB protective drugs.

長崎大学学位論文 学位記番号:博(医歯薬)甲第1192号 学位授与年月日:令和元年12月4日

Author: Ryoma Kayano, Yoichi Morofuji, Shinsuke Nakagawa, Shuji Fukuda, Daisuke Watanabe, Hiroki Ozawa, Masami Niwa, Takayuki Matsuo

Citation: Biochemical and Biophysical Research Communications, 503(3), pp.1885-1890; 2018

Nagasaki University (長崎大学), 博士(医学) (2019-12-04)

http://hdl.handle.net/10069/39582

長崎大学学位論文 [学位記番号]博（医歯薬）甲第1192号 [学位授与年月日]令和元年12月4日

(2019-12-04)