关键词: 血管紧张素II 1型受体阻断剂, 动脉粥样硬化, 肠道菌群, 氧化三甲胺

Abstract: AIM: To investigate the effect of telmisartan on intestinal flora and metabolite TMAO in atherosclerosis. METHODS: Seventeen ApoE-/-mice were randomly divided into two groups: a control group (n=8) and a telmisartan (10 mg/kg, intragastric administration) treatment group (n=9). All mice were fed a high-fat diet. After 12 weeks, the mice were sacrificed. Venous blood was collected from the retro-orbital sinus to detect TMAO using high-performance liquid phase chromatography-tandem mass spectrometry. The severity of atherosclerosis was determined by measuring the area of the plaque at the root of the aorta. The plaque stability was determined by analyzing the expression of interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1) and macrophage infiltration in plaques and plaque morphology. Colonic fecal 16S- RNA V3-V4 region sequencing was used to analyze intestinal flora. RESULTS: Compared with the control group, the plaque area of the telmisartan treatment group decreased significantly, and the expression of IL-6, MCP-1, and infiltration macrophages also decreased significantly. Plasma TMAO levels were significantly lower in the telmisartan-treated group than in the control group. Meanwhile, the blood pressure and body weight of the mice treated with telmisartan were lower than those of the control group. Intestinal flora analysis showed that telmisartan significantly changed the composition of intestinal flora and reduced six bacteria known to produce TMAO, including Anaeroplasmataceae, Bacteroidaceae, Clostridiaceae, Lachnospiraceae, Ruminococcaceae, and Proteus. CONCLUSION: In addition to blocking AT1R, telmisartan may reduce TMAO plasma content by changing intestinal flora composition.

Key words: angiotensin Ⅱ type 1 receptor blocker, atherosclerosis, intestinal microecology, trimethylamine oxide