EGb761 improves the cognitive function of elderly db/db(-/-) diabetic mice by regulating the beclin-1 and NF-κB signaling pathways.
EGb761 improves the cognitive function of elderly db/db(-/-) diabetic mice by regulating the beclin-1 and NF-κB signaling pathways.
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EGb761通过调节beclin-1和NF-κB信号通路改善老年db/db-/-糖尿病小鼠的认知功能
DOI：
10.1007/s11011-018-0295-2
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发表时间：
2018-12
影响因子：
3.6
通讯作者：
Zhou HG
中科院分区：
文献类型：
--
作者：
Guan ZF;Zhang XM;Tao YH;Zhang Y;Huang YY;Chen G;Tang WJ;Ji G;Guo QL;Liu M;Zhang Q;Wang NN;Yu ZY;Hao-Yang;Wu GF;Tang ZP;Du ZG;Shang XL;Liu YC;Mei GH;Guo JC;Zhou HG
评估EGb 761是否可以保护患有认知障碍的老年糖尿病小鼠，并探讨beclin-1介导的自噬在这些保护作用中的作用。将2个月大的雄性db/db−/−小鼠和野生型C57/BL 6小鼠随机分为6组：db/db−/−对照组、db/db−/− 50 mg组、db/db−/− 100 mg组、野生型（WT）对照组、WT 50 mg组和WT 100 mg组。从6月龄开始，每天一次灌胃给予EGb 761（50 mg/kg或100 mg/kg体重），持续1个月。8个月时进行Y型迷宫和社会选择测验。测量血压。使用磁共振成像（MRI）测量大脑中的成像变化。采用免疫组化和Western blotting方法检测Beclin-1、LC 3和NF-κB的表达和分布。透射电镜观察海马超微结构改变。与WT小鼠相比，db/db−/−小鼠的学习能力、记忆和整体认知功能下降（P < 0.05），EGb 761可显著改善db/db−/−小鼠的学习记忆功能（P < 0.05）。EGb 761显著改善db/db−/−小鼠的收缩压（P < 0.01）。此外，与WT相比，fMRI-粗体显示db/db−/−组小鼠海马体下降。EGb 761可改善上述变化。免疫组织化学染色和蛋白质印迹证实，EGb 761显著增加db/db−/−小鼠脑中beclin-1的水平，降低LC 3-II/I的水平（P < 0.05）。db/db−/−组NF-κB水平明显高于WT组，EGb 761显著降低db/db−/−小鼠NF-κB水平（P < 0.05）。db/db−/−小鼠自噬体有增加的趋势，但EGb 761对自噬体的数量无明显影响。与正常的老龄WT小鼠相比，老龄db/db−/−小鼠有更常见的脑小血管疾病和认知功能障碍并发症。EGb 761可通过可能涉及调节beclin-1、LC 3和NF-κB的机制显著改善衰老db/db−/−小鼠的认知功能。
To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db−/− mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db−/− control, db/db−/− 50 mg, db/db−/− 100 mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100 mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6 months. Y-maze and social choice tests were performed at 8th months. The blood pressure was measured. The imaging changes in the brain were measured using magnetic resonance imaging (MRI). The expression and distribution of beclin-1, LC3, and NF-κB were detected using immunohistochemistry staining and western blotting. Ultrastructure alterations in the hippocampus were observed using transmission electron microscopy. Compared with WT mice, the learning ability, memory and overall cognitive function of db/db−/− mice decreased (P < 0.05), and EGb761 could significantly improve the learning and memory function of db/db−/− mice (P < 0.05). EGb761 significantly improved systolic blood pressure in db/db−/− mice (P < 0.01). In addition, fMRI-bold showed a decline in the hippocampus of mice in the db/db−/− group compared with WT. EGb761 could improve these above changes. Immunohistochemistry staining and western blotting confirmed that EGb761 significantly increased beclin-1 and reduced LC3-II/I levels in the brains of db/db−/− mice (P < 0.05). NF-κB levels were obviously higher in the db/db−/− group than that in the WT group, and EGb761 significantly reduced NF-κB levels in db/db−/− mice (P < 0.05). There was a trend of increased autophagosomes in db/db−/− mice, but EGb761 did not change obviously the number of autophagosomes. Compared with normal aged WT mice, aging db/db−/− mice had more common complications of cerebral small vessel disease and cognitive dysfunction. EGb761 could significantly improve the cognitive function of aging db/db−/− mice via a mechanism that may involve the regulation of beclin-1, LC3, and NF-κB.
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影响因子：
32.4
作者：
Hubbard-Lucey, Vanessa M.;Shono, Yusuke;Maurer, Katie;West, Mallory L.;Singer, Natalie V.;Ziegler, Carly G. K.;Lezcano, Cecilia;Motta, Ana Carolina Fragoso;Schmid, Karin;Levi, Samuel M.;Murphy, George F.;Liu, Chen;Winkler, Jeffrey D.;Amaravadi, Ravi K.;Rogler, Gerhard;Dickinson, Anne M.;Holler, Ernst;van den Brink, Marcel R. M.;Cadwell, Ken
通讯作者：
Cadwell, Ken
影响因子：
4.4
作者：
Burda, J;Matiasová, M;Burda, R
通讯作者：
Burda, R
影响因子：
--
作者：
MILES, RM
通讯作者：
MILES, RM
Beclin-1介导的自噬可能与链脲佐菌素诱导的糖尿病小鼠老年认知和情感障碍有关
影响因子：
12.6
作者：
Guan ZF;Zhou XL;Zhang XM;Zhang Y;Wang YM;Guo QL;Ji G;Wu GF;Wang NN;Yang H;Yu ZY;Zhou HG;Guo JC;Liu YC
通讯作者：
Liu YC
影响因子：
7.7
作者：
Janson, J;Laedtke, T;Butler, PC
通讯作者：
Butler, PC