Gastrodin Attenuates Bilateral Common Carotid Artery Occlusion-Induced Cognitive Deficits via Regulating Aβ-Related Proteins and Reducing Autophagy and Apoptosis in Rats.
Gastrodin Attenuates Bilateral Common Carotid Artery Occlusion-Induced Cognitive Deficits via Regulating Aβ-Related Proteins and Reducing Autophagy and Apoptosis in Rats.
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DOI：
10.3389/fphar.2018.00405
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发表时间：
2018
影响因子：
5.6
通讯作者：
Shi JS
中科院分区：
文献类型：
--
作者：
Liu B;Gao JM;Li F;Gong QH;Shi JS
天麻素（Gastrodin，GAS）是从天麻中提取的一种有效成分，在中国被用于治疗缺血性中风、癫痫、头晕和痴呆已有数百年的历史。本研究探讨其对血管性痴呆（VD）的作用及其分子机制。采用双侧颈总动脉结扎法建立VD模型。BCCAO手术后共7天，连续28天口服GAS（15、30和60 mg/kg）以评价治疗效果。Morris水迷宫测试大鼠认知功能。苏木精-伊红染色观察神经元形态学变化。流式细胞术检测细胞凋亡。Western blot检测目的蛋白的表达。结果显示，BCCAO可导致大鼠认知功能障碍、海马CA 1和CA 3区锥体神经元损伤、β-淀粉样蛋白（Aβ）沉积、自噬过度和细胞凋亡。GAS治疗显著改善BCCAO诱导的认知障碍和海马神经元损伤。分子生物学分析表明，GAS可能通过降低Aβ1-40/42、APP和β位点APP裂解酶1的表达水平，增加Aβ相关蛋白、去整合素和金属蛋白酶10和胰岛素降解酶的表达而发挥保护作用。同时，GAS通过降低Beclin-1、LC 3-II和p62水平来抑制过度的自噬。GAS还通过下调Bax和上调Bcl-2的表达来抑制细胞凋亡。P38 MAPK信号通路参与了这一过程。GAS通过靶向Aβ相关蛋白的形成，抑制海马神经元的自噬和凋亡，对BCCAO诱导的VD有治疗作用。
Gastrodin (GAS), an active constituent extracted from Gastrodia elata Blume, is used to treat ischemic stroke, epilepsy, dizziness, and dementia for centuries in China. This study examined its effects on vascular dementia (VD) and the underlying molecular mechanisms. VD was established by ligation of bilateral common carotid artery occlusion (BCCAO). A total of 7 days after BCCAO surgery, GAS (15, 30, and 60 mg/kg) was orally administered for 28 consecutive days to evaluate therapeutic effects. Cognitive function was tested by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin–Eosin staining. Flow cytometry was used for evaluating apoptosis in the hippocampi. The target protein expression was examined by Western blot. The results showed that BCCAO induced cognitive impairment, hippocampus CA1 and CA3 pyramidal neuron damage, beta-amyloid (Aβ) deposition, excessive autophagy, and apoptosis. GAS treatment significantly improved BCCAO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that GAS exerted the protective effect via reducing the levels of Aβ1–40/42, APP, and β-site APP-cleaving enzyme 1 expression, and increasing Aβ-related protein, a disintegrin and metalloprotease 10, and insulin degrading enzyme expression. Meanwhile, GAS inhibited excessive autophagy via decreasing Beclin-1, LC3-II, and p62 levels. Furthermore, GAS inhibited apoptosis through the downregulation of Bax and upregulation of Bcl-2. Moreover, P38 MAPK signaling pathway was involved in the process. Our findings demonstrate that GAS was effective in the treatment of BCCAO-induced VD via targeting Aβ-related protein formation and inhibiting autophagy and apoptosis of hippocampus neurons.
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影响因子：
8.3
作者：
Choi, Bo-Ryoung;Lee, Sang Rim;Kim, Hahn Young
通讯作者：
Kim, Hahn Young
影响因子：
15.1
作者：
Kukreja L;Kujoth GC;Prolla TA;Van Leuven F;Vassar R
通讯作者：
Vassar R
影响因子：
3.7
作者：
Gao C;Li S;Zhao T;Chen J;Ren H;Zhang H;Wang X;Lang M;Liu J;Gao S;Zhao X;Sheng J;Yuan Z;Hao J
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Hao J
影响因子：
7.8
作者：
Ghatan, S;Larner, S;Kinoshita, Y;Hetman, M;Patel, L;Xia, Z;Youle, R J;Morrison, R S
通讯作者：
Morrison, R S
影响因子：
4.4
作者：
Cai, Zhiyou;Liu, Zhou;Tian, Fuming
通讯作者：
Tian, Fuming