Tian Ayong, Ma Xiaochuan, Li Hui, Zhang Rongwei
Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Department of Gerontology and Geriatrics, The Third Hospital of Shenyang, Shenyang, Liaoning 110001, P.R. China.
Exp Ther Med. 2020 Mar;19(3):1940-1946. doi: 10.3892/etm.2019.8402. Epub 2019 Dec 31.
Dl-3n-butylphthalide (NBP) has been reported to be a beneficial and promising drug for the treatment and prevention of vascular dementia (VD). NBP has been demonstrated to improve learning and memory in rats with vascular cognitive impairment by activating the silent information regulator 1/brain-derived neurotrophic factor pathway. However, NBP is a multi-target drug. Therefore, the present study aimed to determine whether the protective effects of NBP on learning deficits in a rat model of VD were due to the inhibition of autophagy via the phosphorylated mammalian target of rapamycin (p-mTOR) pathway. NBP treatment attenuated memory damage in rats with VD, as demonstrated by T-maze and Morris water maze tests. NBP administration also significantly reduced the levels of the characteristic autophagic proteins Beclin 1 and LC3II and upregulated phosphorylation levels of mTOR at Ser-2448 compared with the VD group. However, treatment of rats with VD with NBP plus the mTOR inhibitor rapamycin failed to significantly suppress Beclin 1 and LC3II expression. These results suggested that the beneficial effects of NBP on learning deficits in a rat model of VD were due to the suppression of ischemia-induced autophagy via the p-mTOR signaling pathway.
据报道，丁苯酞（NBP）是一种用于治疗和预防血管性痴呆（VD）的有益且有前景的药物。通过激活沉默信息调节因子1/脑源性神经营养因子通路，NBP已被证明可改善血管性认知障碍大鼠的学习和记忆能力。然而，NBP是一种多靶点药物。因此，本研究旨在确定NBP对VD大鼠模型学习缺陷的保护作用是否归因于通过磷酸化雷帕霉素靶蛋白（p-mTOR）通路抑制自噬。如T迷宫和莫里斯水迷宫试验所示，NBP治疗减轻了VD大鼠的记忆损伤。与VD组相比，NBP给药还显著降低了自噬特征蛋白Beclin 1和LC3II的水平，并上调了mTOR在Ser-2448位点的磷酸化水平。然而，用NBP加mTOR抑制剂雷帕霉素治疗VD大鼠未能显著抑制Beclin 1和LC3II的表达。这些结果表明，NBP对VD大鼠模型学习缺陷的有益作用归因于通过p-mTOR信号通路抑制缺血诱导的自噬。
