Mortensen P B, Holtug K, Bonnén H, Clausen M R
Department of Medicine A, Rigshospitalet, University of Copenhagen, Denmark.
Gastroenterology. 1990 Feb;98(2):353-60. doi: 10.1016/0016-5085(90)90825-l.
Short-chain (C2-C5) fatty acids account for 60%-70% of the anions in the colon. Acetate (C2) is nontoxic in contrast to C(3)4-C5 fatty acids (propionate, butyrate, isobutyrate, valerate, and isovalerate), which induce coma in animals and may be important in the pathogenesis of hepatic coma in humans. An in-vitro fecal incubation system was used to map out short-chain fatty acid production in the presence of lactulose, amino acids, albumin, or blood. Albumin and blood increased production of all C2-C5 fatty acids. In contrast, lactulose was converted to acetate only and increased fecal acidity. The degradation of amino acids, albumin, and blood to short-chain fatty acids was completely inhibited by 10-25 mM lactulose. This was caused mainly by the acidifying effect of lactulose. pH-independent inhibition of blood and amino acid degradation to short-chain fatty acids required concentrations of lactulose exceeding 50-100 mM. Thus, the effect of lactulose in the treatment of hepatic coma may be related to its rapid fermentation into organic acids at rates exceeding colonic buffering capacity. This probably reduces formation of toxic fatty acids and ammonia from amino acids, polypeptides, and blood in the colon.
短链（C2 - C5）脂肪酸占结肠中阴离子的60% - 70%。与C3 - C5脂肪酸（丙酸、丁酸、异丁酸、戊酸和异戊酸）不同，乙酸（C2）无毒，C3 - C5脂肪酸可使动物昏迷，可能在人类肝昏迷的发病机制中起重要作用。采用体外粪便培养系统来测定在存在乳果糖、氨基酸、白蛋白或血液的情况下短链脂肪酸的产生。白蛋白和血液会增加所有C2 - C5脂肪酸的产生。相比之下，乳果糖仅转化为乙酸并增加粪便酸度。10 - 25 mM的乳果糖可完全抑制氨基酸、白蛋白和血液降解为短链脂肪酸。这主要是由乳果糖的酸化作用引起的。pH值无关的对血液和氨基酸降解为短链脂肪酸的抑制作用需要乳果糖浓度超过50 - 100 mM。因此，乳果糖在治疗肝昏迷中的作用可能与其以超过结肠缓冲能力的速率快速发酵为有机酸有关。这可能会减少结肠中由氨基酸、多肽和血液产生的有毒脂肪酸和氨的形成。
