Dias V C, Madsen K L, Yatscoff R W, Doring K, Thomson A B
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
Transplantation. 1994 Dec 15;58(11):1241-6.
The effect on intestinal nutrient transport of the immunosuppressive drugs cyclosporin A (CsA), cyclosporin G (CsG), and rapamycin (RAP) was determined in New Zealand white rabbits. Rabbits received oral doses of CsA (20 mg/kg/day), CsG (10 mg/kg/day), or RAP (1 mg/kg/day) for 10 days. Animals receiving RAP had decreased food intake and weight gain compared with controls. This correlated with a decrease in both total ileal weight and corresponding mucosal weight. CsA and CsG administration had no effect on food intake, total weight gain, or intestinal weight. Villus surface area was significantly decreased in all groups as compared with controls. Jejunal uptake of D-glucose as well as 1 medium and 4 long chain fatty acids was not affected by drug administration, while both mucosal-to-serosal and net 3-0-methylglucose fluxes were increased (P < 0.05) in the jejunum by all 3 drugs. In the ileum, the rates of uptake of D-glucose as well as stearic and linoleic acids were increased in animals treated with RAP compared with controls. There was an increase in the ileal values of the maximal transport rate (Vmax) and apparent Michaelis constant (Km*) in RAP, and a fall in the Vmax and Km* in CsG. CsG administration resulted in a decreased cholesterol uptake in both jejunum and ileum, and a decreased D-glucose uptake in the ileum compared with controls. These differences in glucose uptake among groups could not be attributed to variations in body, intestinal, or mucosal weights. It is unlikely that the changes observed in CsA- and CsG-treated animals would have nutritional importance, as these animals gained weight normally. In addition, in these animals the changes mainly occurred in the ileum, not in the jejunum, where most glucose is absorbed, and the associated alterations in the values of the Vmax and Km* would lead to reciprocal changes in the rates of uptake of varying luminal concentrations of glucose. In contrast, these changes are likely to be of more importance in RAP-treated animals, since they failed to gain weight normally. The significance of these findings needs to be established in chronically treated animals.
在新西兰白兔中测定了免疫抑制药物环孢素A（CsA）、环孢素G（CsG）和雷帕霉素（RAP）对肠道营养物质转运的影响。兔子口服CsA（20毫克/千克/天）、CsG（10毫克/千克/天）或RAP（1毫克/千克/天），持续10天。与对照组相比，接受RAP的动物食物摄入量和体重增加减少。这与回肠总重量和相应黏膜重量的减少相关。给予CsA和CsG对食物摄入量、总体重增加或肠道重量没有影响。与对照组相比，所有组的绒毛表面积均显著减少。空肠对D - 葡萄糖以及1种中链脂肪酸和4种长链脂肪酸的摄取不受药物给药的影响，而所有3种药物均使空肠黏膜到浆膜以及净3 - O - 甲基葡萄糖通量增加（P < 0.05）。在回肠中，与对照组相比，接受RAP治疗的动物中D - 葡萄糖以及硬脂酸和亚油酸的摄取速率增加。RAP组回肠的最大转运速率（Vmax）和表观米氏常数（Km*）值增加，而CsG组的Vmax和Km下降。与对照组相比，给予CsG导致空肠和回肠胆固醇摄取减少，回肠D - 葡萄糖摄取减少。各组间葡萄糖摄取的这些差异不能归因于体重、肠道或黏膜重量的变化。在CsA和CsG治疗的动物中观察到的变化不太可能具有营养重要性，因为这些动物体重正常增加。此外，在这些动物中，变化主要发生在回肠，而非大部分葡萄糖吸收的空肠，并且Vmax和Km值的相关改变将导致不同管腔葡萄糖浓度摄取速率的相反变化。相比之下，这些变化在接受RAP治疗的动物中可能更重要，因为它们体重未能正常增加。这些发现的意义需要在长期治疗的动物中确定。
