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PNAS:肠道微生物群信号可能调控血压

来源:EurekAlert! 2013-02-12 20:12

一项研究发现,通过对两个主要的短链脂肪酸(SCFAs)受体——嗅觉受体78 (Olfr78)和Gpr41起作用,肠道微生物群产生的短链脂肪酸(SCFAs)可能在调控血压方面起到作用。

Jennifer L. Pluznick及其同事发现,Olfr78在肾脏中表达,并且会响应短链脂肪酸(SCFAs),特别是响应丙酸盐,而介导肾素分泌。当给小鼠提供丙酸盐的时候,它们的血压会出现幅度大而迅速的基于剂量依赖的下降,而敲除了Olfr78 的小鼠对这种效应特别敏感,这提示Olfr78的正常功能是提高血压并对抗短链脂肪酸(SCFAs)的低血压效应。相比之下,缺乏Gpr41基因的小鼠对丙酸盐没有低血压响应,而这个剂量导致了野生类型的小鼠的强烈低血压响应,这提示Gpr41参与到了对丙酸盐做出响应降低血压。通过给予抗生素而减少Olfr78被敲除小鼠的肠道微生物群生物质导致了它们的血压增加,这提示肠道微生物群制造的丙酸盐通过Olfr78受体调控血压。

这组作者提出,研究肠道微生物群和肾脏-心血管系统的串扰可能有助于更好地理解和治疗高血压。(生 物 谷Bioon.com)

Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation

Jennifer L. Pluznick, Ryan J. Protzko, Haykanush Gevorgyan, Zita Peterlin, Arnold Sipos, Jinah Han, Isabelle Brunet, La-Xiang Wan, Federico Rey, Tong Wang, Stuart J. Firestein, Masashi Yanagisawa, Jeffrey I. Gordon, Anne Eichmann, Janos Peti-Peterdi, and Michael J. Caplan

Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.

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