一項(xiàng)研究發(fā)現(xiàn)，通過對(duì)兩個(gè)主要的短鏈脂肪酸（SCFAs）受體——嗅覺受體78 (Olfr78)和Gpr41起作用,，腸道微生物群產(chǎn)生的短鏈脂肪酸（SCFAs）可能在調(diào)控血壓方面起到作用,。
Jennifer L. Pluznick及其同事發(fā)現(xiàn)，Olfr78在腎臟中表達(dá),，并且會(huì)響應(yīng)短鏈脂肪酸（SCFAs）,，特別是響應(yīng)丙酸鹽，而介導(dǎo)腎素分泌,。當(dāng)給小鼠提供丙酸鹽的時(shí)候,，它們的血壓會(huì)出現(xiàn)幅度大而迅速的基于劑量依賴的下降，而敲除了Olfr78 的小鼠對(duì)這種效應(yīng)特別敏感,，這提示Olfr78的正常功能是提高血壓并對(duì)抗短鏈脂肪酸（SCFAs）的低血壓效應(yīng),。相比之下，缺乏Gpr41基因的小鼠對(duì)丙酸鹽沒有低血壓響應(yīng),，而這個(gè)劑量導(dǎo)致了野生類型的小鼠的強(qiáng)烈低血壓響應(yīng),，這提示Gpr41參與到了對(duì)丙酸鹽做出響應(yīng)降低血壓。通過給予抗生素而減少Olfr78被敲除小鼠的腸道微生物群生物質(zhì)導(dǎo)致了它們的血壓增加,，這提示腸道微生物群制造的丙酸鹽通過Olfr78受體調(diào)控血壓,。
這組作者提出，研究腸道微生物群和腎臟-心血管系統(tǒng)的串?dāng)_可能有助于更好地理解和治療高血壓,。(生 物 谷Bioon.com)
doi: 10.1073/pnas.1215927110
PMC:
PMID:
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.
