Charach G, Rabinovich P D, Konikoff F M, Grosskopf I, Weintraub M S, Gilat T
Department of Internal Medicine C, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel.
J Med. 1998;29(3-4):125-36.
In most patients with atherosclerosis, the underlying metabolic derangement remains undefined. Animal experiments have suggested that the ability to produce and excrete large amounts of bile acids may be an adaptation mechanism to cholesterol overload protecting against the atherogenic effects of cholesterol. However, there are very few data on bile acid excretion in human atherosclerosis. In the present study, we have investigated fecal bile acid secretion in subjects with and without coronary artery disease. The target group consisted of 30 patients with proven coronary artery disease and the control group consisted of 27 matched subjects without clinical or laboratory evidence of coronary atherosclerosis. Fecal bile acids were measured by gas-liquid chromatography from 24-hr stool collections under a controlled diet. The patients excreted significantly less bile acids than the controls (325+/-135 vs. 592+/-223 mg/day, respectively, p < 0.0001). The difference was primarily due to a reduced excretion of secondary bile acids. Less than 50% of deoxycholate was excreted by patients (180+/-81 mg/day) as compared to controls (367+/-168 mg/day, p < 0.0002), while lithocholic acid excretion was 111+/-62 mg/day in patients vs. 190 +/-70 mg/day in controls (p < 0.005). The fecal output of the two primary bile acids, cholic and chenodeoxycholic acid, did not differ significantly between patients and controls. The fecal output of total bile acids correlated with that of both secondary bile acids in patients as well as in controls. These findings suggest that patients with coronary heart disease are unable to excrete adequate amounts of bile acids to rid themselves of excess cholesterol, even if they are able to maintain a plasma cholesterol level comparable to that of healthy controls.
在大多数动脉粥样硬化患者中，潜在的代谢紊乱仍不明确。动物实验表明，大量产生和排泄胆汁酸的能力可能是一种针对胆固醇过载的适应机制，可抵御胆固醇的致动脉粥样硬化作用。然而，关于人类动脉粥样硬化中胆汁酸排泄的数据非常少。在本研究中，我们调查了有和没有冠状动脉疾病的受试者的粪便胆汁酸分泌情况。目标组由30例经证实患有冠状动脉疾病的患者组成，对照组由27例匹配的受试者组成，这些受试者没有冠状动脉粥样硬化的临床或实验室证据。在控制饮食的情况下，通过气液色谱法对24小时粪便样本中的胆汁酸进行测量。患者排泄的胆汁酸明显少于对照组（分别为325±135与592±223毫克/天，p<0.0001）。这种差异主要是由于次级胆汁酸排泄减少。与对照组（367±168毫克/天，p<0.0002）相比，患者排泄的脱氧胆酸盐不到50%（180±81毫克/天），而患者中石胆酸的排泄量为111±62毫克/天，对照组为190±70毫克/天（p<0.005）。两种初级胆汁酸，即胆酸和鹅去氧胆酸的粪便排出量在患者和对照组之间没有显著差异。患者和对照组中总胆汁酸的粪便排出量与次级胆汁酸的排出量均相关。这些发现表明，冠心病患者即使能够维持与健康对照组相当的血浆胆固醇水平，也无法排泄足够量的胆汁酸以清除多余的胆固醇。
