高血压是心血管疾病的主要危险因素,其分子和细胞机制仍有待阐明。大量研究显示,肠道内生菌调节血压稳态。前期实验室通过血浆代谢谱学测序发现了普通拟杆菌(Bacteroides vulgatus)可以增加高盐饮食高血压小鼠血浆中的腺苷含量,同时可能影响小鼠高血压进程。该研究首先验证B.vulgatus对血浆腺苷含量和高盐饮食小鼠血压的影响。随后,为了夯实谱学结果、寻找血浆中腺苷的来源并解析B.vulgatus促进腺苷合成的机制,研究对B.vulgatus灌胃小鼠机体合成腺苷的重要场所之一——小肠上皮细胞进行了基因表达谱分析。结果发现,B.vulgatus灌胃小鼠的小肠上皮细胞中一系列差异表达的基因与小鼠的核苷酸、能量、蛋白质等物质的代谢过程相关。从差异表达的基因中遴选了与腺苷合成紧密相关的基因,并验证了其蛋白质表达水平。结果发现,腺苷合成过程中的关键蛋白质CD39在B.vulgatus灌胃后的小鼠小肠上皮细胞中表达显著增加。更进一步,小鼠小肠上皮细胞中CD39表达的增加与小鼠血浆中腺苷含量呈正相关性。综上,B.vulgatus在调节高盐饮食小鼠的高血压进程中,升高了血浆腺苷的含量,并伴随着小肠上皮细胞CD39的表达上调,且二者存在相关性。该研究结果为阐明内生菌调节心血管健康的机理提供了一定的理论依据。
Hypertension is one of the risk factors for cardiovascular disease, and its molecular and cellular mechanisms remain to be elucidated. Numerous studies have shown that intestinal endophytes regulate vascular homeostasis. Previously, metabolomics study in our laboratory suggested that Bacteroides vulgatus increased the plasma adenosine concentration in high-salt diet mice, and such adenosine may alleviate the process of hypertension. In this study, we validated the change of plasma adenosine concentration by B. vulgatus treatment, and showed anti-hypertensive effect of B. vulgatus in high-salt diet mice. To find the source of adenosine in plasma, B. vulgatus treated intestinal epithelial cells were analyzed for gene expression profiling, because they are one of the important sites for adenosine synthesis. As a result, a series of genes were differentially expressed in the intestinal epithelial cells with B. vulgatus treatment. Further, these genes were enriched in cellular metabolic processes of nucleotides, energy and proteins, and included genes closely related to adenosine synthesis. the expression of CD39, a key protein in adenosine synthesis, were then validated. CD39 significantly increased in mouse intestinal epithelial cells after B. vulgatus gavage. Further, CD39 expression in intestinal epithelial cells was positively correlated with plasma adenosine concentration. In conclusion, this study showed that B. vulgatus increased plasma adenosine content and regulated hypertension in mice with a high-salt diet. Further, CD39 expression was increased by B. vulgatus in intestinal epithelial cells, and it was positively correlated with plasma adenosine concentration. These results may provide a theoretical basis for elucidating the relationship between intestinal endophytes and cardiovascular health.
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