Lee T K, Cardona M A, Kurkchubasche A G, Smith S D, Mueller A R, Lee K K, Rowe M I, Schraut W H
Department of Surgery, University of Pittsburgh, Pennsylvania 15261.
J Surg Res. 1992 Jun;52(6):605-14. doi: 10.1016/0022-4804(92)90137-o.
A short course of FK 506 after small bowel transplantation averts rejection in the rat and achieves indefinite survival of the recipient whose nutritional status is dependent on the function of the intestinal graft. Ex vivo electrophysiologic studies using the Ussing Cell were conducted to delineate functional competence of the graft by evaluating mucosal ion transport and glutamine utilization. Orthotopic small-bowel transplantation was performed in Lewis (LEW) rats as recipients of either Brown-Norway (BN) allografts or LEW syngeneic grafts. Allograft recipients received FK 506 either as a short course (2 mg/kg on Day 0-4 after transplantation) or continuously (2 mg/kg Day 0-4, then 0.5 mg/kg weekly). Ileal mucosa was harvested from small bowel grafts 9 and 60 days after transplantation and mounted in the Ussing Cell containing Hanks' balanced salt solution with/without L-glutamine (20 mM). Transmembrane potential difference (PD), which represents mucosal active ion transport, and mucosal resistance, an index of membrane integrity, were recorded. Nine days after transplantation, mucosal PD was the same in the ileum from syngeneic grafts, allografts treated with FK 506 and normal LEW and BN rats, and the addition of glutamine increased PD equally in all groups. In comparison, PD was markedly decreased in allografts undergoing rejection, and the glutamine response was blunted. Sixty days after transplantation, mucosal PD was reduced in allografts treated with a short course of FK 506, but normal in allografts receiving continuous immunosuppression with FK 506 and in syngeneic grafts. A decrease of mucosal resistance was not a feature of rejection nor a sequel of limited FK 506 therapy. Our data indicate that allograft rejection results in a significant decrease in mucosal PD and a poor response to glutamine. Control of rejection by FK 506 preserves normal electrophysiologic responses of the allograft mucosa.
小肠移植后短期使用FK 506可避免大鼠发生排斥反应，并使营养状况依赖于肠移植功能的受体实现长期存活。通过使用尤斯灌流小室进行体外电生理研究，以评估黏膜离子转运和谷氨酰胺利用情况，从而描绘移植肠的功能状态。将原位小肠移植到Lewis（LEW）大鼠体内，受体分别接受Brown-Norway（BN）同种异体移植物或LEW同基因移植物。同种异体移植物受体接受FK 506治疗，分为短期疗程（移植后第0 - 4天给予2 mg/kg）或持续给药（第0 - 4天给予2 mg/kg，然后每周给予0.5 mg/kg）。在移植后9天和60天从小肠移植物中采集回肠黏膜，并安装在含有/不含有L - 谷氨酰胺（20 mM）的Hanks平衡盐溶液的尤斯灌流小室中。记录代表黏膜主动离子转运的跨膜电位差（PD）以及作为膜完整性指标的黏膜电阻。移植后9天，同基因移植物、接受FK 506治疗的同种异体移植物以及正常LEW和BN大鼠回肠的黏膜PD相同，添加谷氨酰胺后所有组的PD均同等增加。相比之下，正在发生排斥反应的同种异体移植物中PD显著降低，且谷氨酰胺反应减弱。移植后60天，接受短期FK 506治疗的同种异体移植物中黏膜PD降低，但接受FK 506持续免疫抑制的同种异体移植物和同基因移植物中的黏膜PD正常。黏膜电阻降低不是排斥反应的特征，也不是有限FK 506治疗的后遗症。我们的数据表明，同种异体移植物排斥反应会导致黏膜PD显著降低以及对谷氨酰胺反应不佳。通过FK 506控制排斥反应可保留同种异体移植物黏膜的正常电生理反应。
