Liu Hong, Zhong Lili, Zhang Yuwei, Liu Xuewei, Li Ji
a Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, P.R. China.
b Postdoctoral Program, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, P.R. China.
Biochem Cell Biol. 2018 Oct;96(5):672-681. doi: 10.1139/bcb-2017-0209. Epub 2018 Feb 8.
Rutin, a flavonoid glycoside, has been reported to exert neuroprotective effects. Loss of endogenous estrogen and dysregulation of the estrogen receptor (ER) signaling pathway are associated with the increased risk of stroke in women after menopause. This study was performed to investigate whether rutin could protect against cerebral ischemia by modulating the ER pathway. Ovariectomized (OVX) rats were given intraperitoneal injections of vehicle (dimethyl sulfoxide), rutin (100 mg/kg body mass) or 17β-estradiol (100 μg/kg body mass) for 5 consecutive days. Then, the rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h followed by a 24 h reperfusion to establish the cerebral ischemia-reperfusion (I/R) injury. We found that rutin improved the sensorimotor performance and recognition memory of rats subjected to I/R, decreased the infarct size, and attenuated neuron loss. Rutin treatment also increased the levels of ERα, ERβ, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), tropomyosin receptor kinase A (TrkA), TrkB, and phospho-cAMP-responsive element binding protein (p-CREB) in rat hippocampus and cerebral cortex. The protective effects of rutin were comparable to that of 17β-estradiol, and were partially blocked by ICI182780, an ER antagonist. The above results suggest that rutin preconditioning ameliorates cerebral I/R injury in OVX rats through ER-mediated BDNF-TrkB and NGF-TrkA signaling.
芦丁是一种黄酮糖苷，据报道具有神经保护作用。内源性雌激素的丧失和雌激素受体（ER）信号通路的失调与绝经后女性中风风险增加有关。本研究旨在探讨芦丁是否能通过调节ER通路来预防脑缺血。对去卵巢（OVX）大鼠连续5天腹腔注射溶剂（二甲基亚砜）、芦丁（100mg/kg体重）或17β-雌二醇（100μg/kg体重）。然后，对大鼠进行大脑中动脉闭塞（MCAO）1小时，随后再灌注24小时，以建立脑缺血再灌注（I/R）损伤模型。我们发现，芦丁改善了I/R大鼠的感觉运动性能和认知记忆，减小了梗死面积，并减轻了神经元损失。芦丁处理还增加了大鼠海马和大脑皮层中ERα、ERβ、脑源性神经营养因子（BDNF）、神经生长因子（NGF）、原肌球蛋白受体激酶A（TrkA）、TrkB和磷酸化环磷酸腺苷反应元件结合蛋白（p-CREB）的水平。芦丁的保护作用与17β-雌二醇相当，并被ER拮抗剂ICI182780部分阻断。上述结果表明，芦丁预处理通过ER介导的BDNF-TrkB和NGF-TrkA信号通路改善OVX大鼠的脑I/R损伤。
