短链脂肪酸丁酸抑制动脉粥样硬化形成及其分子机制

本研究通过观察丁酸对动脉粥样硬化斑块形成以及肠道组织结构和功能的影响,探讨丁酸防治动脉粥样硬化的效应及可能机制.选取8周龄雄性载脂蛋白E基因敲除(apolipoprotein E-knockout,ApoE-/-)小鼠,随机分成对照组(高脂高胆固醇饲料+饮水中给予200 mmol/L氯化钠,n = 10)和丁酸组(高脂...

Short-chain fatty acid butyrate acid attenuates atherosclerotic plaque formation in apolipoprotein E-knockout mice and the underlying mechanism

This study was designed to evaluate the role of short-chain fatty acid butyrate acid on intestinal morphology and function,and atherosclerotic plaque formation in apolipoprotein E-knockout(ApoE-/-)mice.ApoE-/-mice on high-fat,high-cholesterol diet were treated with butyrate acid(200 mmol/L)or NaCl(control)in the drinking water for 12 weeks,followed by histological evaluations of atherosclerotic lesion in aorta.Real-time PCR analysis and ELISA were used to measure the expression levels of proinflammatory cytokines.Butyrate acid significantly attenuated high-fat,high-cholesterol diet-induced atherosclerotic plaque formation in ApoE-/-mice.Butyrate acid prevented high-fat,high-cholesterol diet-induced inflammation in both the aorta and the circulation,as evidenced by reduced expression of proinflammatory cytokines.These changes were accompanied by a marked attenuation in metabolic endotoxemia lipopolysaccharide(LPS).Butyrate acid induced intestinal expression of the tight junction proteins(Occludin and zona occuldens protein-1),thereby preventing the gut permeability.Butyrate acid dose-dependently upregulated the expression of the tight junction proteins in Caco-2 cells in GPR41-dependent manner.In conclusion,butyrate acid attenuates atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation through restoration of the gut barrier.