Halsted C H, Grayer D I, Luebbers E H, Yardley J H, Hendrix T R
Gut. 1971 Apr;12(4):262-7. doi: 10.1136/gut.12.4.262.
Since intestinal fluid production in experimental cholera can be limited by cycloheximide, an inhibitor of protein synthesis, the same agent was used to determine whether there are similar mechanisms for fluid production in response to an osmotic gradient. Intestinal fluid production was measured by perfusion of paired rabbit jejunal loops (10 cm) in vivo, in controls, and in animals receiving 20 mg/kg intravenous cycloheximide one hour before perfusion. In each animal one loop was perfused with isotonic Ringer's lactate and the other with a hypertonic glucose-Ringer's lactate solution, 563 mOsm/litre. In control animals mean fluid production in the hypertonic loop was seven times that in the isotonic loop. Cycloheximide decreased the fluid response to the hypertonic stimulus by one half (p < 0.001). In a separate measurement of bidirectional sodium fluxes, using sodium(22), it was shown that the decreased net sodium movement into the lumen observed after cycloheximide was the result of decreased flux from blood to lumen. The major histological alteration after cycloheximide was on the crypt epithelial cells with sparing of villus crests. Glucose absorption was unaffected. These data parallel the observed effect of cycloheximide on cholera exotoxin induced secretion, suggesting that a process requiring continued protein synthesis is also necessary for the intestinal fluid response to an osmotic gradient.
由于蛋白质合成抑制剂放线菌酮可限制实验性霍乱中的肠液分泌，因此使用该药物来确定在对渗透梯度作出反应时，是否存在类似的肠液分泌机制。通过对成对的兔空肠袢（10厘米）进行体内灌注来测量肠液分泌，一组为对照组，另一组为在灌注前一小时静脉注射20毫克/千克放线菌酮的动物组。在每只动物中，一个肠袢用等渗乳酸林格液灌注，另一个用563毫渗量/升的高渗葡萄糖 - 乳酸林格液灌注。在对照动物中，高渗肠袢中的平均肠液分泌量是等渗肠袢的七倍。放线菌酮使对高渗刺激的肠液反应降低了一半（p < 0.001）。在另一项使用钠（22）对双向钠通量的测量中，结果显示，放线菌酮处理后观察到的进入肠腔的净钠移动减少是由于从血液到肠腔的通量减少所致。放线菌酮处理后的主要组织学改变发生在隐窝上皮细胞，而绒毛顶部未受影响。葡萄糖吸收未受影响。这些数据与放线菌酮对霍乱毒素诱导分泌的观察结果相似，表明对于肠液对渗透梯度的反应，一个需要持续蛋白质合成的过程也是必需的。
