Yin Junjun, Yang Jiehong, Zhao Buchang, Zhao Chao, Fu Wei, He Yu, Zeng Miaolin, Yang Yuting, Wei Xiaoyu, Ding Zhishan, Bai Jingxian, Wan Haitong, Zhou Huifen
Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
Buchang Pharmaceutical Co., Ltd., Xi'an, China.
Evid Based Complement Alternat Med. 2022 Sep 21;2022:4016935. doi: 10.1155/2022/4016935. eCollection 2022.
The traditional Chinese medicines of Buyang Huanwu decoction (BYHW), Naoxintong capsule (NXT), and Yangyin Tongnao granules (YYTN) have excellent effects in preventing and treating cerebrovascular disease and are widely tolerated by patients. However, their effects on middle cerebral artery occlusion (MCAO) remain unknown.
We evaluated gut microbiota alterations, the brain transcriptome, and nerve cell responses in rats with MCAO.
Our results showed that BYHW, NXT, and YYTN not only effectively improved the damaged state of blood vessels in rats and restored nerve function, but also improved survival. Additional experiments showed that treatment with BYHW, NXT, and YYTN regulated the intestinal microflora. Transcriptome analyses showed that BYHW, NXT, and YYTN modulated the transcriptome of rats with MCAO. The common mechanism of the three prescriptions for the treatment of cerebral ischemia may be related to the intestinal flora regulation of 60S ribosomal protein L18 (Rpl18), eukaryotic translation initiation factor 3 subunit, Ras homolog family member C, G protein subunit gamma 13 (Gng13), and Gng10 genes, among which Rpl18 is the most important. In addition, the three prescriptions had great specificity as anticerebral ischemia targets. Moreover, BYHW, NXT, and YYTN mitigated MCAO-induced hyperactivation of microglia and astrocytes.
This study provides a foundation for further research on the mechanisms and treatment of IS. The results strongly suggest that key gut microbiota can be used to study functional genomics of brain, leading to novel discoveries about key genes involved in important biological processes.
补阳还五汤（BYHW）、脑心通胶囊（NXT）和养yin通脑颗粒（YYTN）等中药在防治脑血管疾病方面疗效显著，且患者耐受性良好。然而，它们对大脑中动脉闭塞（MCAO）的影响尚不清楚。
我们评估了MCAO大鼠的肠道微生物群变化、脑转录组和神经细胞反应。
我们的结果表明，BYHW、NXT和YYTN不仅有效改善了大鼠血管的损伤状态，恢复了神经功能，还提高了生存率。进一步的实验表明，BYHW、NXT和YYTN治疗可调节肠道微生物群。转录组分析表明，BYHW、NXT和YYTN可调节MCAO大鼠的转录组。这三种方剂治疗脑缺血的共同机制可能与肠道菌群对60S核糖体蛋白L18（Rpl18）、真核翻译起始因子3亚基、Ras同源家族成员C、G蛋白亚基γ13（Gng13）和Gng10基因的调节有关，其中Rpl18最为重要。此外，这三种方剂作为抗脑缺血靶点具有很大的特异性。此外，BYHW、NXT和YYTN减轻了MCAO诱导的小胶质细胞和星形胶质细胞的过度激活。
本研究为进一步研究缺血性脑卒中（IS）的发病机制和治疗提供了基础。结果强烈表明，关键肠道微生物群可用于研究脑功能基因组学，从而发现参与重要生物学过程的关键基因的新发现。
