Sun S, Katz S M, Schechner R S, Tellis V A, Greenstein S M
Department of Surgery, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10467, USA.
Transplantation. 1996 May 27;61(10):1447-50. doi: 10.1097/00007890-199605270-00005.
We have previously reported the adverse effects of cyclosporine on small intestine transplant physiology. In this study, we report for the first time the effect of tacrolimus (FK) on graft intestinal blood flow and intramural distribution, vascular resistance, and absorptive function. Isogeneic small intestine transplantation was performed in Lewis rats. Animals were grouped based upon the following treatment schedules: no treatment for 1 week in group 1; 0.6 ml/kg/day i.m. polyethylene glycol (PEG) for 1 week in group 2; 2 mg/kg/day i.m. FK for 1 week in group 3; 0.6 ml/kg/day PEG for 1 week and then 0.3 ml/kg/day for 5 weeks in group 4; 2 mg/kg/day FK for 1 week and then 1 mg/kg/day for 5 weeks in group 5. Group 6 was the same as in group 5 but FK was withdrawn for 1 week prior to assessment. Maltose absorption was measured to evaluate graft absorptive function. Blood flow and its intramural distribution to mucosal and serosal/muscularis layers were determined using the radioactive microsphere technique. Perfusion pressure was measured to calculate vascular resistance. One week of FK administration in group 3 did not change graft hemodynamics and absorption significantly. Prolonged FK treatment up to 6 weeks in group 5 resulted in a significant increase in mucosal vascular resistance (71.0 +/- 9.6 versus 47.7 +/- 6.7 U/g, P<0.01) and significant decreases in mucosal blood flow (1.14 +/- O.15 versus 1.69 +/- 0.24 ml/g/min, P<0.01) and maltose absorption (30 min after loading. 155.4 +/- 26.9 versus 216.4 +/- 29.6, P<0.01; 60 min after loading: 172.9 +/- 24.5 versus 229.1 +/- 32.6 glucose mg/dl P<0.01). The serosal/muscularis layer remained relatively unaffected. Withdrawal of FK for 1 week after prolonged treatment in group 6 resulted in restorations of all parameters measured to normal ranges. We conclude that a short course of FK is safe, but prolonged FK administration has harmful effects on the hemodynamics and function of small intestinal transplants. Complete recovery is achieved when FK is discontinued.
我们之前曾报道过环孢素对小肠移植生理的不良影响。在本研究中，我们首次报告了他克莫司（FK）对移植肠血流及其壁内分布、血管阻力和吸收功能的影响。在Lewis大鼠中进行了同基因小肠移植。根据以下治疗方案对动物进行分组：第1组1周不治疗；第2组每天肌肉注射0.6 ml/kg聚乙二醇（PEG），共1周；第3组每天肌肉注射2 mg/kg FK，共1周；第4组每天肌肉注射0.6 ml/kg PEG，共1周，然后每天0.3 ml/kg，共5周；第5组每天肌肉注射2 mg/kg FK，共1周，然后每天1 mg/kg，共5周。第6组与第5组相同，但在评估前停用FK 1周。通过测量麦芽糖吸收来评估移植肠的吸收功能。使用放射性微球技术测定血流及其在黏膜和浆膜/肌层的壁内分布。测量灌注压以计算血管阻力。第3组给予FK 1周对移植肠血流动力学和吸收无明显影响。第5组延长FK治疗至6周导致黏膜血管阻力显著增加（71.0±9.6对47.7±6.7 U/g，P<0.01），黏膜血流显著减少（1.14±0.15对1.69±0.24 ml/g/min，P<0.01），麦芽糖吸收减少（负荷后30分钟：155.4±26.9对216.4±29.6，P<0.01；负荷后60分钟：172.9±24.5对229.1±32.6葡萄糖mg/dl，P<0.01）。浆膜/肌层相对未受影响。第6组在长期治疗后停用FK 1周导致所有测量参数恢复到正常范围。我们得出结论，短期使用FK是安全的，但长期使用FK对小肠移植的血流动力学和功能有有害影响。停用FK后可实现完全恢复。
