微生物衍生的醋酸盐可减轻自发性高血压大鼠延髓头端腹外侧区的神经炎症。
Microbiota-derived acetate attenuates neuroinflammation in rostral ventrolateral medulla of spontaneously hypertensive rats.
机构信息
Department of Neurobiology, Hebei Medical University, Shijiazhuang, 050017, China.
Department of Physiology, Hebei Medical University, Shijiazhuang, 050017, China.
出版信息
J Neuroinflammation. 2024 Apr 18;21(1):101. doi: 10.1186/s12974-024-03061-3.
BACKGROUND
Increased neuroinflammation in brain regions regulating sympathetic nerves is associated with hypertension. Emerging evidence from both human and animal studies suggests a link between hypertension and gut microbiota, as well as microbiota-derived metabolites short-chain fatty acids (SCFAs). However, the precise mechanisms underlying this gut-brain axis remain unclear.
METHODS
The levels of microbiota-derived SCFAs in spontaneously hypertensive rats (SHRs) were determined by gas chromatography-mass spectrometry. To observe the effect of acetate on arterial blood pressure (ABP) in rats, sodium acetate was supplemented via drinking water for continuous 7 days. ABP was recorded by radio telemetry. The inflammatory factors, morphology of microglia and astrocytes in rostral ventrolateral medulla (RVLM) were detected. In addition, blood-brain barrier (BBB) permeability, composition and metabolomics of the gut microbiome, and intestinal pathological manifestations were also measured.
RESULTS
The serum acetate levels in SHRs are lower than in normotensive control rats. Supplementation with acetate reduces ABP, inhibits sympathetic nerve activity in SHRs. Furthermore, acetate suppresses RVLM neuroinflammation in SHRs, increases microglia and astrocyte morphologic complexity, decreases BBB permeability, modulates intestinal flora, increases fecal flora metabolites, and inhibits intestinal fibrosis.
CONCLUSIONS
Microbiota-derived acetate exerts antihypertensive effects by modulating microglia and astrocytes and inhibiting neuroinflammation and sympathetic output.
背景
调节交感神经的大脑区域中的神经炎症增加与高血压有关。来自人类和动物研究的新证据表明，高血压与肠道微生物群以及微生物衍生的代谢物短链脂肪酸（SCFAs）之间存在联系。然而，这种肠道-大脑轴的确切机制尚不清楚。
方法
通过气相色谱-质谱法测定自发性高血压大鼠（SHR）中微生物衍生的 SCFAs 水平。为了观察乙酸盐对大鼠动脉血压（ABP）的影响，通过饮用水补充乙酸钠，连续 7 天。通过无线电遥测记录 ABP。检测延髓头端腹外侧区（RVLM）中的炎症因子、小胶质细胞和星形胶质细胞的形态。此外，还测量了血脑屏障（BBB）通透性、肠道微生物组的组成和代谢组学以及肠道的病理表现。
结果
SHR 血清中的乙酸盐水平低于正常血压对照大鼠。补充乙酸盐可降低 ABP，抑制 SHR 的交感神经活性。此外，乙酸盐可抑制 SHR 的 RVLM 神经炎症，增加小胶质细胞和星形胶质细胞形态的复杂性，降低 BBB 通透性，调节肠道菌群，增加粪便菌群代谢物，并抑制肠道纤维化。
结论
微生物衍生的乙酸盐通过调节小胶质细胞和星形胶质细胞以及抑制神经炎症和交感神经输出发挥降压作用。
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