Lu Junjie, Wu Hui, Jin Huan, He Ziyi, Shen Lin, Ma Chen, Xu Xiaojuan, Wang Zixian, Shuai Bo
Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Hubei Province, Xiangyang, China.
Front Pharmacol. 2024 Sep 4;15:1467298. doi: 10.3389/fphar.2024.1467298. eCollection 2024.
Although guidelines support the efficacy of Modified Qing' E Formula (MQEF) in treating postmenopausal osteoporosis (PMOP), its underlying mechanisms remain incompletely understood. This retrospective investigation aims to elucidate MQEF's impact on serum exosomal miRNA expression in postmenopausal osteoporosis patients and to explore potential therapeutic mechanisms.
Following ethical approval and registration, postmenopausal osteoporosis patients aged 50-85 years, meeting the diagnostic criteria were randomly selected and received MQEF decoction supplementary therapy. Serum samples were collected pre- and post-treatment, followed by isolation and sequencing of exosomal miRNAs. Differential miRNAs in serum exosomes were identified, and bioinformatics analysis was conducted to discern the principal exosomal miRNAs involved in MQEF's effects on PMOP and the associated signaling pathways.
Eighteen clinical blood samples were collected. A total of 282,185 target genes were detected across the three groups. 306 miRNAs exhibited altered expression in serum exosomes of PMOP patients, while MQEF intervention resulted in changes in 328 miRNAs. GO enrichment analysis revealed the immune and endocrine systems was pertained. KEGG enrichment analysis indicated associations between PMOP occurrence and MQEF treatment with cytokine interactions, oxidative phosphorylation, and the renin-angiotensin system. Intersectional analysis identified 17 miRNAs, including 2 consistent trends. miR-3188 as a potentially pivotal miRNA implicated in both PMOP occurrence and MQEF treatment.
This study constitutes the first randomized, retrospective clinical exploration confirming that MQEF demonstrates regulatory influence over exosomal miRNA expression in PMOP patients' serum, its impact likely involves modulation of the immune and endocrine systems, as well as the renin-angiotensin system.
尽管指南支持改良青娥方（MQEF）治疗绝经后骨质疏松症（PMOP）的疗效，但其潜在机制仍未完全明确。本回顾性研究旨在阐明MQEF对绝经后骨质疏松症患者血清外泌体miRNA表达的影响，并探索潜在的治疗机制。
经伦理批准和注册后，随机选取年龄在50 - 85岁、符合诊断标准的绝经后骨质疏松症患者，给予MQEF汤剂辅助治疗。在治疗前后采集血清样本，随后进行外泌体miRNA的分离和测序。鉴定血清外泌体中的差异miRNA，并进行生物信息学分析，以识别参与MQEF对PMOP作用的主要外泌体miRNA及其相关信号通路。
共采集18份临床血样。三组共检测到282,185个靶基因。306个miRNA在PMOP患者血清外泌体中的表达发生改变，而MQEF干预导致328个miRNA发生变化。基因本体（GO）富集分析显示与免疫和内分泌系统有关。京都基因与基因组百科全书（KEGG）富集分析表明，PMOP的发生以及MQEF治疗与细胞因子相互作用、氧化磷酸化和肾素 - 血管紧张素系统之间存在关联。交叉分析确定了17个miRNA，其中2个具有一致趋势。miR - 3188作为一个潜在的关键miRNA，与PMOP的发生和MQEF治疗均有关。
本研究是首次随机、回顾性临床探索，证实MQEF对PMOP患者血清外泌体miRNA表达具有调节作用，其影响可能涉及免疫和内分泌系统以及肾素 - 血管紧张素系统的调节。
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