Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui Province, China.
Department of Cardiology, The Second Affiliated Hospital of Wannan Medical College, 10# Kangfu Road, Wuhu, 241000, Anhui Province, China.
Sleep Breath. 2023 Oct;27(5):1769-1777. doi: 10.1007/s11325-023-02781-9. Epub 2023 Jan 31.
To investigate the influence of sacubitril valsartan sodium (SVS) on chronic intermittent hypoxia (IH) related gut microbiome composition alteration and aortic injury.
Experiments were performed using SD rats, which were divided into three groups: control, IH, and SVS group. O concentration was decreased to 7-8% at nadir approximately every 3 min in IH group (8 h per day for 6 weeks) or was left unchanged in control group. Rats in SVS group were orally gavaged with SVS at the dosage of 30 mg/kg/day (2 weeks after chronic IH exposure). At week 6, fecal and aortic samples were harvested for 16 s rDNA analysis and histological analysis, respectively.
Principal coordinate analysis and non-metric multidimensional scaling analysis indicated that the bacterial community was altered by chronic IH exposure, while SVS treatment restored the intestinal microbial communities. Further analysis showed that IH decreased the relative abundance of Lactobacillus and Prevotella, while rats treated with SVS was enriched with Firmicutes, Bacilli, Prevotellaceae, and Lactobacillus, which was similar to control rats. Immunohistochemical staining showed that SVS prevented the upregulation of transforming growth factor-β1 and tumor necrosis factor-alpha in the aorta.
SVS prevented aortic adverse response to IH, possibly through modulating intestinal microbiota.
研究沙库巴曲缬沙坦钠（SVS）对慢性间歇性低氧（IH）相关肠道微生物群落组成改变和主动脉损伤的影响。
采用 SD 大鼠进行实验，分为三组：对照组、IH 组和 SVS 组。IH 组每隔 3 分钟左右将 O 浓度降低至 7-8%（每天 8 小时，持续 6 周），对照组则保持不变。SVS 组大鼠在慢性 IH 暴露后第 2 周开始每日口服 SVS 30mg/kg（6 周）。第 6 周时，采集粪便和主动脉样本进行 16s rDNA 分析和组织学分析。
主坐标分析和非度量多维尺度分析表明，慢性 IH 暴露改变了细菌群落，而 SVS 治疗恢复了肠道微生物群落。进一步分析表明，IH 降低了乳杆菌和普雷沃氏菌的相对丰度，而 SVS 治疗组厚壁菌门、芽孢杆菌科、乳杆菌属丰度增加，与对照组相似。免疫组化染色显示，SVS 可预防转化生长因子-β1 和肿瘤坏死因子-α在主动脉中的上调。
SVS 可预防 IH 引起的主动脉不良反应，可能通过调节肠道微生物群。
