Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats.
Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats.
复制标题
小檗碱通过调节 DM 大鼠的异常炎症反应和胰岛素信号通路改善糖尿病相关的认知衰退
DOI：
10.3389/fphar.2017.00334
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发表时间：
2017
影响因子：
5.6
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Chen Q;Mo R;Wu N;Zou X;Shi C;Gong J;Li J;Fang K;Wang D;Yang D;Wang K;Chen J
背景：记忆障碍是糖尿病患者的常见特征之一。糖尿病脑组织慢性炎症介质的释放和胰岛素抵抗导致了毒性因子Aβ42的产生，而Aβ42是阿尔茨海默病的标志物。此外，糖尿病记忆障碍也主要与内侧前额叶皮层（mPFC）葡萄糖的摄取/代谢有关。以前，小檗碱（BBr）的抗炎和降血糖作用已被描述在外周组织。为了更好地了解BBr对糖尿病患者认知行为的影响，我们研究了BBr在糖尿病大鼠前额叶皮层抗炎和改善胰岛素抵抗中的作用。方法：采用BBr（187.5mg/Kg/d）灌胃法建立糖尿病大鼠模型。采用恐惧状态法进行认知功能评价，采用western-blot检测相关蛋白表达。采用正电子发射断层成像技术检测糖尿病大鼠前额叶皮层葡萄糖摄取。通过商业ELISA试剂盒测定炎症介质的水平。结果：BBr可抑制糖尿病大鼠mPFC炎症介质释放，降低胰岛素抵抗。Bbr还下调PI 3 K/Akt/mTOR和MAPK信号通路的激活，以及两种新型亚型PKCη和PKC的激活以及神经元中NF-κB的移位;此外，神经元特异性葡萄糖转运蛋白GLUT 3与糖尿病组相比显着增加2-3倍;同时，Bbr还促进脑中葡萄糖的摄入。此外，BBr降低淀粉样前体蛋白和BACE-1的表达以及寡聚体Aβ42的产生。最后，它加速了信息的强化，改善了认知障碍。结论：BBr可抑制糖尿病大鼠mPFC炎症通路的激活和胰岛素抵抗。改善糖尿病大鼠认知功能的损害。
Background: Memory-impairment was one of the common characteristics in patients with diabetes mellitus. The release of chronic inflammation mediators and insulin resistance in diabetic brain gave rise to the generation of toxic factor Aβ42 which was the marker of Alzheimer’s disease. In addition, the impairment of memory in diabetes mellitus was also correlated predominantly with uptake/metabolism of glucose in medial prefrontal cortex (mPFC). Previously, anti-inflammation and hypoglycemic effects of berberine (BBr) have been described in peripheral tissues. For better understanding the effects of BBr on cognitive action in diabetics, we investigated the functions of BBr involved in anti-inflammation and ameliorating insulin resistance in prefrontal cortex of diabetic rats. Methods: Intragastric administration of BBr (187.5 mg/Kg/d) was used in diabetic rats. Fear-condition assay was applied for cognitive assessment, and relative protein expressions were detected by western-blot. The glucose uptake in prefrontal cortex of diabetic rats was tested by Positron-Emission Tomography imaging. The levels of inflammation mediators were determined by commercial ELISA kits. Results: The inflammation mediator release and insulin resistance in the mPFC of diabetic rats was inhibited by BBr. The activation of PI3K/Akt/mTOR and MAPK signaling pathway, as well as two novel isoforms PKCη and PKC𝜀 and the translocation of NF-κB in neuron were also down-regulated by BBr; furthermore, the neuron specific glucose transporter GLUT3 was remarkably augmented by 2–3 times when compared with diabetic group; meanwhile, BBr also promoted glucose uptake in the brain. Additionally BBr decreased the expressions of amyloid precursor protein and BACE-1, and the production of oligomeric Aβ42. Finally, it accelerates the reinforcement of the information and ameliorates cognitive impairment. Conclusion: BBr inhibited the activation of inflammation pathway and insulin resistance in the mPFC of diabetic rats. Finally, it improved the lesion of cognition in diabetic rats.