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粪便微生物群移植通过改变自发性高血压大鼠的肠道微生物群组成和肠黏膜屏障功能来调节血压。

Fecal Microbiota Transplantation Regulates Blood Pressure by Altering Gut Microbiota Composition and Intestinal Mucosal Barrier Function in Spontaneously Hypertensive Rats.

作者信息

Xu Xinghua, Jin Hua, Li Xiaoling, Yan Chunlu, Zhang Qiuju, Yu Xiaoying, Liu Zhijun, Liu Shuangfang, Zhu Feifei

机构信息

Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China.

The Second Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China.

出版信息

Probiotics Antimicrob Proteins. 2024 Aug 22. doi: 10.1007/s12602-024-10344-x.

Abstract

Hypertension is accompanied by gut microbiota imbalance, but the role of bacteria in the pathogenesis of hypertension requires further study. In this study, we used fecal microbiota transplantation to determine the impact of microbiota composition on blood pressure in spontaneous hypertensive rats (SHRs), using normotensive Wistar Kyoto (WKY) rats as controls. SHRs were randomly divided into two groups (n = 10/group), SHR and SHR-T (SHR plus fecal transplantation) and WKY into WKY and WKY-T (WKY plus fecal transplantation). SHR-T received fecal transplantation from WKY, while WKY-T received fecal transplantation from SHR. Blood pressure was measured from the tail artery in conscious rats. 16S rDNA gene amplicon sequencing was used to analyze bacterial composition. Circulating levels of diamine oxidase, D-lactate, FITC-Dextrans, and lipopolysaccharide were determined. Hematoxylin and eosin (H&E) staining was used to observe structural changes in the intestinal mucosa. Immunofluorescence, Western blot, and RT-PCR were utilized to determine changes in the expression of tight junction proteins. Following cross fecal transplantation, blood pressure decreased in SHR and increased in WKY. Significant differences in gut microbial composition were found between hypertensive and normotensive rats, specifically regarding the relative abundance of lactic and butyric acid-producing bacteria. Changes in gut microbiota composition also impacted the intestinal mucosal barrier integrity. Moreover, fecal transplantation affected the expression of tight junction proteins that may impact intestinal mucosal permeability and structural integrity. Blood pressure may be associated with butyric acid-producing intestinal microbiota and its function in regulating the integrity of intestinal mucosal barrier.

摘要

高血压伴有肠道微生物群失衡,但细菌在高血压发病机制中的作用仍需进一步研究。在本研究中,我们采用粪便微生物群移植来确定微生物群组成对自发性高血压大鼠(SHR)血压的影响,以血压正常的Wistar Kyoto(WKY)大鼠作为对照。SHR被随机分为两组(每组n = 10),即SHR组和SHR-T组(SHR加粪便移植组),WKY大鼠分为WKY组和WKY-T组(WKY加粪便移植组)。SHR-T组接受来自WKY的粪便移植,而WKY-T组接受来自SHR的粪便移植。在清醒大鼠的尾动脉测量血压。使用16S rDNA基因扩增子测序分析细菌组成。测定二胺氧化酶、D-乳酸、异硫氰酸荧光素-葡聚糖和脂多糖的循环水平。采用苏木精-伊红(H&E)染色观察肠黏膜的结构变化。利用免疫荧光、蛋白质免疫印迹和逆转录-聚合酶链反应来确定紧密连接蛋白表达的变化。交叉粪便移植后,SHR的血压降低,WKY的血压升高。高血压大鼠和血压正常大鼠之间的肠道微生物组成存在显著差异,特别是在产乳酸和丁酸细菌的相对丰度方面。肠道微生物群组成的变化也影响了肠黏膜屏障的完整性。此外,粪便移植影响了紧密连接蛋白的表达,这可能会影响肠黏膜通透性和结构完整性。血压可能与产丁酸的肠道微生物群及其调节肠黏膜屏障完整性的功能有关。

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