目标:已知长期暴露于低温会升高血压,导致一种称为冷诱发高血压(CIH)的疾病。我们之前的研究表明肠道微生物群改变之间的相关性,丁酸水平降低,以及CIH的发生和进展然而,丁酸盐在CIH中的作用及其潜在机制需要进一步研究.
方法:我们将无特定病原体(SPF)大鼠暴露于持续寒冷温度(4±1°C)6周以建立aCIH大鼠模型。将大鼠按剂量和持续时间分为不同组,每天给予大鼠丁酸盐(0.5或1g/kg/天)。我们评估了高血压相关的表型,病理形态学变化,和棕色脂肪组织(BAT)的内分泌相关表型。通过16sRNA测序和非靶向代谢组学评估丁酸盐对肠道菌群和肠道内容物代谢的影响,分别。
结果:冷暴露组大鼠的收缩压(SBP)明显低于冷暴露组。丁酸可能会增加物种,丰度,和大鼠肠道菌群的多样性。具体来说,丁酸盐干预丰富了有益菌属,如乳酸杆菌科,并降低了有害细菌属的水平,如放线菌和赤霉科。冷暴露显着增加BAT细胞和线粒体数量。补充丁酸后,过氧化物酶体增殖物激活受体γ-共激活剂1a和成纤维细胞生长因子21水平显著升高(P<0.05),脂滴的体积和数量增加。Cold组的ANGII和高密度脂蛋白水平升高,但在补充丁酸盐后降低。
结论:丁酸可能通过促进细菌的生长和BAT产生的有益衍生因子的分泌来降低CIH的血压,从而缓解感冒引起的血压升高。这项研究证明了丁酸盐的抗高血压作用及其潜在的治疗机制,为在寒冷环境中生活或工作的人群中CIH的预防和治疗提供了新的见解。
OBJECTIVE: Chronic exposure to cold temperature is known to elevate blood pressure, leading to a condition known as cold-induced hypertension (CIH). Our previous research suggested correlations between alterations in gut microbiota, decrease in butyrate level, and the onset and progression of CIH. However, the role of butyrate in CIH and the underlying mechanisms need further investigation.
METHODS: We exposed Specific Pathogen Free (SPF) rats to continuous cold temperature (4 ± 1 °C) for 6 weeks to establish a CIH rat model. Rats were divided into different groups by dose and duration, and the rats under cold were administered with butyrate (0.5 or 1 g/kg/day) daily. We assessed hypertension-associated phenotypes, pathological morphological changes, and endocrine-related phenotypes of brown adipose tissue (BAT). The effects of butyrate on gut microbiota and intestinal content metabolism were evaluated by 16s RNA sequencing and non-targeted metabolomics, respectively.
RESULTS: The systolic blood pressure (SBP) of rats exposed to cold after supplemented with butyrate were significantly lower than that of the Cold group. Butyrate may increase the species, abundance, and diversity of gut microbiota in rats. Specifically, butyrate intervention enriched beneficial bacterial genera, such as Lactobacillaceae, and decreased the levels of harmful bacteria genera, such as Actinobacteriota and Erysipeiotrichaceae. Cold exposure significantly increased BAT cells and the number of mitochondria. After butyrate supplementation, the levels of peroxisome proliferator-activated receptor gamma coactivator 1a and fibroblast growth factor 21 in BAT were significantly elevated (P < 0.05), and the volume and number of lipid droplets increased. The levels of ANG II and high-density lipoprotein were elevated in the Cold group but decreased after butyrate supplementation.
CONCLUSIONS: Butyrate may attenuate blood pressure in CIH by promoting the growth of beneficial bacteria and the secretion of beneficial derived factors produced by BAT, thus alleviating the elevation of blood pressure induced by cold. This study demonstrates the anti-hypertensive effects of butyrate and its potential therapeutic mechanisms, offering novel insights to the prevention and treatment of CIH in populations living or working in cold environments.