Angong Niuhuang Pill ameliorates cerebral ischemia/reperfusion injury in mice partly by restoring gut microbiota dysbiosis.
Angong Niuhuang Pill ameliorates cerebral ischemia/reperfusion injury in mice partly by restoring gut microbiota dysbiosis.
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安宫牛黄丸通过恢复肠道菌群失调改善小鼠脑缺血/再灌注损伤
DOI：
10.3389/fphar.2022.1001422
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
安宫牛黄丸（ANP）是著名的中成药，用于治疗缺血性或出血性中风已有数百年的历史。然而，ANP在脑卒中治疗中的作用机制却鲜有报道。随着越来越多的证据表明急性缺血性卒中与肠道微生物群改变之间存在机制联系，本研究旨在从肠道微生物群的角度确定ANP治疗急性缺血性卒中的作用机制。建立小鼠大脑中动脉闭塞（MCAO）急性缺血性中风模型，对假手术组、模型组和ANP治疗组MCAO小鼠盲肠内容物进行16 S核糖体RNA（rRNA）基因测序和代谢组学分析。结果表明，ANP显著改善脑梗死体积，改善神经功能缺损，减少缺血侧皮质、海马和纹状体的组织病理学损伤。后者的影响包括抑制神经元死亡，增加尼氏体，减少细胞凋亡。此外，ANP通过调节细菌的丰度来逆转肠道微生物群的生态失调，所述细菌的作用可以减轻MCAO损伤，例如拟杆菌门和厚壁菌门、毛螺菌科和普雷沃菌科以及Alloprevotella和Roseburia属。与炎症和神经保护相关的微生物代谢产物，如前列腺素I2和尿苷，也受到ANP治疗的调节。尿苷、鸟苷和肌苷可能是ANP治疗组肠道微生物群产生的潜在神经调质。斯皮尔曼相关分析表明，这些代谢产物与Alloprevotella、Lachnoclostridium、Enterorhabdus、Roseburia、Lachnospiraceae_UCG-006和Colidextribacter等属密切相关。我们的研究结果表明，减轻肠道微生物群失调是ANP预防缺血性卒中的机制之一，并表明靶向Aloprevotella，Lachnoclostridium，Enterorhabdus，Roseburia，Lachnospiraceae_UCG-006和Colidextribacter可能是潜在的抗卒中治疗。
Angong Niuhuang Pill (ANP) is a famous traditional Chinese patent medicine and is used for treating ischemic or hemorrhagic stroke for centuries. However, the mechanism of action of ANP in stroke treatment has rarely been reported. With increasing evidence for a mechanistic link between acute ischemic stroke and gut microbiota alterations, this study aimed to determine the mechanism of action of ANP in treating acute ischemic stroke from the perspective of the gut microbiota. A mouse model of acute ischemic stroke by middle cerebral artery occlusion (MCAO) was established, and 16S ribosomal RNA (rRNA) gene sequencing and metabolomic analysis were performed on the cecal content samples collected from the sham, model, and ANP-treated MCAO mice. The results showed that ANP significantly ameliorated cerebral infarct volume, improved neurological deficits, and reduced histopathological injuries in the ipsilateral ischemic cortex, hippocampus, and striatum. The latter effects included inhibition of neuronal death, increased Nissl bodies, and decreased cell apoptosis. Moreover, ANP reversed gut microbiota dysbiosis by modulating the abundance of bacteria whose effects may mitigate MCAO damage, such as the phyla Bacteroidetes and Firmicutes, the families Lachnospiraceae and Prevotellaceae, and the genera Alloprevotella and Roseburia. Microbial metabolites related to inflammation and neuroprotection, such as prostaglandin I2 and uridine, were also regulated by ANP treatment. Uridine, guanosine, and inosine might be potential neuromodulators produced by the gut microbiota in the ANP-treated group. Spearman correlation analysis revealed that these metabolites were intimately related to certain genera, including Alloprevotella, Lachnoclostridium, Enterorhabdus, Roseburia, Lachnospiraceae_UCG-006, and Colidextribacter. Our results demonstrated that alleviating gut microbiota dysbiosis is one of the mechanisms by which ANP protects against ischemic stroke and suggest that targeting Alloprevotella, Lachnoclostridium, Enterorhabdus, Roseburia, Lachnospiraceae_UCG-006, and Colidextribacter might be a potential anti-stroke therapy.
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影响因子：
4.7
作者：
Dal-Cim, Tharine;Ludka, Fabiana K.;Tasca, Carla I.
通讯作者：
Tasca, Carla I.
影响因子：
4.8
作者：
Ling Y;Gong T;Zhang J;Gu Q;Gao X;Weng X;Liu J;Sun J
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影响因子：
5.6
作者：
Cui H;Cai Y;Wang L;Jia B;Li J;Zhao S;Chu X;Lin J;Zhang X;Bian Y;Zhuang P
通讯作者：
Zhuang P
影响因子：
64.8
作者：
Chouchani, Edward T.;Pell, Victoria R.;Gaude, Edoardo;Aksentijevic, Dunja;Sundier, Stephanie Y.;Robb, Ellen L.;Logan, Angela;Nadtochiy, Sergiy M.;Ord, Emily N. J.;Smith, Anthony C.;Eyassu, Filmon;Shirley, Rachel;Hu, Chou-Hui;Dare, Anna J.;James, Andrew M.;Rogatti, Sebastian;Hartley, Richard C.;Eaton, Simon;Costa, Ana S. H.;Brookes, Paul S.;Davidson, Sean M.;Duchen, Michael R.;Saeb-Parsy, Kourosh;Shattock, Michael J.;Robinson, Alan J.;Work, Lorraine M.;Frezza, Christian;Krieg, Thomas;Murphy, Michael P.
通讯作者：
Murphy, Michael P.
影响因子：
4.6
作者：
Gao Qiang;Han Zhen-Yun;Ma Da-Yong
通讯作者：
Ma Da-Yong