Gibson S W, Valente J F, Alexander J W, Custer D A, Babcock G F, Ogle C K
Department of Surgery, College of Medicine, University of Cincinnati, Ohio 45267, USA.
J Heart Lung Transplant. 1999 Mar;18(3):185-9. doi: 10.1016/s1053-2498(98)00033-3.
Immunosuppressive drugs continue to pose significant risks such as infection, toxicity, or neoplasia when used in long-term therapy. The investigation of newer and safer combined treatment strategies that decrease the need for these drugs is becoming increasingly important. Immunonutrients are known to have significant modulating effects on the immune system. Feeding with Impact, a commercially available diet enriched with arginine, omega-3 fatty acids, and RNA, recently has been shown to extend rat cardiac allograft survival when combined with a donor-specific transfusion (DST) and cyclosporine A (CsA). Because mycophenolate mofetil (MMF) is now commonly used in the clinical setting, the current study was designed to examine the effect on rat cardiac allograft survival when MMF was added to this immunosuppressive regimen.
Intra-abdominal ACI to Lewis heterotopic cardiac allografts were performed. Study groups included untreated controls and recipients receiving varying combinations of a DST (1 mL) on the day prior to engraftment, MMF 45 mg/kg/day from the day of transplant through postoperative day six, and CsA 10 mg/kg on the day prior to operation and 2.5 mg/kg from the day of transplant through postoperative day 6. Animals were fed ad libitum with Impact diet or standard lab chow. Graft survival was determined by cessation of a palpable heartbeat.
Treatment with MMF led to a prolonged allograft survival over historical untreated controls. The combination of MMF with a donor-specific transfusion, Impact, or CsA was associated with an increase in graft survival over MMF alone. The addition of Impact to the combination of MMF and CsA resulted in further improvement. The most pronounced graft survival advantage was seen when Impact was combined with a DST and both of the immunosuppressive agents. One quarter of the animals in this group had a palpable donor heart beat at greater than 150 days, indicating functional tolerance in those animals.
The administration of Impact diet to treatment groups in this study was associated with graft survival advantages when compared to most of the other study groups receiving a similar drug regimen and standard chow. These findings support the importance of nutritional influences on allograft survival, and highlight the potential of diet therapy when used with short courses of clinically relevant immunosuppressive drugs.
免疫抑制药物在长期治疗中持续带来重大风险，如感染、毒性或肿瘤形成。研究更新且更安全的联合治疗策略以减少对这些药物的需求变得愈发重要。已知免疫营养物质对免疫系统具有显著的调节作用。最近研究表明，给予Impact（一种富含精氨酸、ω-3脂肪酸和RNA的商业饮食），与供体特异性输血（DST）和环孢素A（CsA）联合使用时，可延长大鼠心脏移植的存活时间。由于霉酚酸酯（MMF）目前在临床中常用，本研究旨在探讨将MMF添加到该免疫抑制方案中对大鼠心脏移植存活的影响。
进行腹腔内ACI到Lewis的异位心脏移植。研究组包括未治疗的对照组以及在移植前一天接受不同组合治疗的受体，即DST（1 mL）、从移植日至术后第6天给予MMF 45 mg/kg/天，以及在手术前一天给予CsA 10 mg/kg，并从移植日至术后第6天给予2.5 mg/kg。动物自由采食Impact饮食或标准实验室饲料。通过可触及的心跳停止来确定移植物存活。
与既往未治疗的对照组相比，MMF治疗可延长移植存活时间。MMF与供体特异性输血、Impact或CsA联合使用时，移植存活时间比单独使用MMF有所增加。在MMF和CsA联合治疗中添加Impact可进一步改善移植存活情况。当Impact与DST以及两种免疫抑制剂联合使用时，移植物存活优势最为明显。该组四分之一的动物在超过150天时仍可触及供体心脏跳动，表明这些动物具有功能耐受。
与大多数接受类似药物方案和标准饲料的其他研究组相比，本研究中给治疗组给予Impact饮食与移植物存活优势相关。这些发现支持了营养对移植存活影响的重要性，并突出了饮食疗法与短期临床相关免疫抑制药物联合使用时的潜力。
