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
作者：
Zian Xia;Weijun Peng;Shunhua Cheng;Bingwu Zhong;Chenxia Sheng;Chunhu Zhang;Wei Gong;Shuai Cheng;Jun Li;Zhe Wang
神经炎症是阿尔茨海默病 (AD) 发病机制的核心。我们之前证明脑灵汤（NLD）是一种中药，通过抑制 IL-10205 和 IL-6 的表达来有效治疗 AD。在本研究中，我们通过脑室内注射A02051-42肽建立了AD大鼠模型，并评估了NLD治疗的剂量依赖性效应。通过 Morris 水迷宫测试评估，NLD 治疗的大鼠认知功能显着改善。高尔基-考克斯染色显示，NLD 治疗剂量依赖性地增加了 CA1 区域的树突棘，而在媒介物治疗的大鼠中，树突棘减少了。此外，NLD 治疗使海马嗜铬蛋白 A 水平正常化，该水平因 A02051-42 诱导而升高。 NLD 还减弱 A02051-42 诱导的小胶质细胞和星形胶质细胞的活化。随后，NLD 通过抑制 NF-0202B 信号通路和海马中 ASC 依赖性炎症小体，剂量依赖性地降低 TNF-02±、IL-10205 和 IL-6 的水平。这些研究结果表明，NLD 是一种有前途的治疗剂，可在 AD 诱导的神经炎症网络内的多个位点发挥抑制作用。
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-10205 and IL-6. In the present study, we generated the rat model of AD by injecting A02051-42 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 A02051-42 induction. NLD also attenuated activation of microglia and astrocytes induced by A02051-42. Subsequently, NLD dose-dependently reduced levels TNF-02±, IL-10205 and IL-6 by inhibiting the NF-0202B 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.