Wang Zhiwei, Han Yanfen, Tian Shujuan, Bao Junqiang, Wang Yahui, Jiao Junping
Department of Internal Medicine-Neurology, The First Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province 050031, People's Republic of China.
Department of Internal Medicine-Neurology, The Affiliated Hospital of Sergeant School of Army Medical University, Shijiazhuang City, Hebei Province 050000, People's Republic of China.
Neuropsychiatr Dis Treat. 2020 Jun 2;16:1381-1390. doi: 10.2147/NDT.S237406. eCollection 2020.
BACKGROUND/AIM: This study aimed to investigate the effect and mechanism of lupeol on cerebral ischemia-reperfusion injury in rats.
The effects of lupeol on cerebral infarction, cerebral water content, neurological symptoms and cerebral blood flow in rats were evaluated. Nissl staining was carried out to assess the neuronal damage of ischemic brain after I/R in rats. Apoptosis of ischemic brain neurons after I/R was detected by TUNEL staining. Western blotting was carried out to detect the effects of lupeol on the expression of p-PDK1, p-Akt, pc-Raf, p-BAD, cleaved caspase-3 and p-PTEN.
Lupeol significantly increased cerebral blood flow after I/R in rats, reduced brain water content and infarct volume, and decreased neurological function scores. It significantly reduced neuronal damage after I/R in rats, and significantly reduced neuronal cell loss. PI3K inhibitor (LY294002) can eliminate the effect of lupeol on I/R in rats. In addition, lupeol significantly increased the protein expression of p-PDK1, p-Akt, pc-Raf, p-BAD, and down-regulated the expression of cleaved caspase-3. LY294002 reversed the effects of lupeol on the expression of PI3K/Akt signaling pathway-related proteins and cleaved caspase-3 after I/R in rats.
Lupeol had significant neuroprotective effects on brain I/R injury and neuronal apoptosis, and its mechanism may be related to the activation of PI3K/Akt signaling pathway.
背景/目的：本研究旨在探讨羽扇豆醇对大鼠脑缺血再灌注损伤的影响及机制。
评估羽扇豆醇对大鼠脑梗死、脑含水量、神经症状和脑血流量的影响。进行尼氏染色以评估大鼠缺血再灌注后缺血脑区的神经元损伤。采用TUNEL染色检测缺血再灌注后缺血脑神经元的凋亡。进行蛋白质印迹法检测羽扇豆醇对p-PDK1、p-Akt、pc-Raf、p-BAD、裂解的半胱天冬酶-3和p-PTEN表达的影响。
羽扇豆醇显著增加大鼠缺血再灌注后的脑血流量，降低脑含水量和梗死体积，并降低神经功能评分。它显著减少大鼠缺血再灌注后的神经元损伤，并显著减少神经元细胞丢失。PI3K抑制剂（LY294002）可消除羽扇豆醇对大鼠缺血再灌注的影响。此外，羽扇豆醇显著增加p-PDK1、p-Akt、pc-Raf、p-BAD的蛋白表达，并下调裂解的半胱天冬酶-3的表达。LY294002逆转了羽扇豆醇对大鼠缺血再灌注后PI3K/Akt信号通路相关蛋白和裂解的半胱天冬酶-3表达的影响。
羽扇豆醇对脑缺血再灌注损伤和神经元凋亡具有显著的神经保护作用，其机制可能与激活PI3K/Akt信号通路有关。
