Naoling decoction restores cognitive function by inhibiting the neuroinflammatory network in a rat model of Alzheimer's disease.
Naoling decoction restores cognitive function by inhibiting the neuroinflammatory network in a rat model of Alzheimer's disease.
复制标题
脑灵汤通过抑制阿尔茨海默病大鼠模型的神经炎症网络恢复认知功能
DOI：
10.18632/oncotarget.17337
复制
发表时间：
2017-06-27
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Xia Z;Peng W;Cheng S;Zhong B;Sheng C;Zhang C;Gong W;Cheng S;Li J;Wang Z
神经炎症是阿尔茨海默病(AD)发病机制的核心。我们先前的研究表明，中药脑灵汤通过抑制IL-1β和IL-6的表达而发挥抗阿尔茨海默病作用。在本研究中，我们通过侧脑室注射Aβ1-42肽的方法建立AD大鼠模型，并评价其治疗的剂量依赖效应。通过Morris水迷宫测试，NLD组大鼠的认知功能有了显著的改善。高尔基-考克斯染色显示，NLD治疗剂量依赖地增加了CA1区的树突棘，而在赋形剂治疗的大鼠中树突棘减少了。此外，NLD治疗使海马区嗜铬粒蛋白A水平正常化，而Aβ1-42诱导的嗜铬粒蛋白A水平升高。NLD还可减弱Aβ1-42诱导的小胶质细胞和星形胶质细胞的激活。随后，NLD通过抑制NF-αB信号通路和海马区Asc依赖的炎症体，呈剂量依赖性地降低肿瘤坏死因子-β、IL-1κ和IL-6的水平。这些发现表明，NLD是一种有前景的治疗药物，它在AD诱导的神经炎性网络中的多个部位发挥抑制作用。
Neuroinflammation is central to the pathogenesis of Alzheimer's disease (AD). We previously showed that Naoling decoction (NLD), a traditional Chinese medicine, was effective against AD, acting by inhibiting expression of IL-1β and IL-6. In the present study, we generated the rat model of AD by injecting Aβ1–42 peptide intracerebroventricularly and evaluated the dose-dependent effects of NLD treatment. The NLD-treated rats exhibited significant improvements in cognitive function as evaluated by the Morris water maze test. Golgi-Cox staining revealed that NLD treatment dose-dependently increased dendritic spines in the CA1 region, which were diminished in vehicle-treated rats. Further, NLD treatment normalized hippocampal Chromogranin A levels, which were elevated by Aβ1-42 induction. NLD also attenuated activation of microglia and astrocytes induced by Aβ1-42. Subsequently, NLD dose-dependently reduced levels TNF-α, IL-1β and IL-6 by inhibiting the NF-κB signaling pathway and the ASC-dependent inflammasome in the hippocampus. These findings reveal that NLD is a promising therapeutic agent that exerts inhibitory effects at multiple sites within the neuroinflammatory network induced in AD.
登录
查看更多内容
影响因子：
--
作者：
Baek H;Ye M;Kang GH;Lee C;Lee G;Choi DB;Jung J;Kim H;Lee S;Kim JS;Lee HJ;Shim I;Lee JH;Bae H
通讯作者：
Bae H
影响因子：
6.1
作者：
Edison, Paul;Archer, Hilary A.;Brooks, David J.
通讯作者：
Brooks, David J.
影响因子：
3.9
作者：
Lechner, T;Adlassnig, C;Marksteiner, J
通讯作者：
Marksteiner, J
影响因子：
9.3
作者：
Couturier J;Stancu IC;Schakman O;Pierrot N;Huaux F;Kienlen-Campard P;Dewachter I;Octave JN
通讯作者：
Octave JN
影响因子：
5.4
作者：
Lin L;Ni B;Lin H;Zhang M;Li X;Yin X;Qu C;Ni J
通讯作者：
Ni J