TLSF_(JM)联合小剂量FK506促进大鼠小肠移植耐受

Effect of TLSF_(JM) Associated with Small Dose of FK506 on The Immunosuppression in Rat Small Bowel Transplantation

目的探讨TLSFJM(JM急性T淋巴细胞白血病细胞分泌的抑制因子)作为抑制因子对小肠移植急性排斥反应的抑制效应及其机理,并与FK506的抑制效应特点和副作用进行比较分析。方法雄性BN和LEW大鼠分别作为供、受体行小肠移植,共分5组:小肠移植组(SBT组)、大剂量FK506〔0.5mg/(kg.d)〕组、小剂量FK506〔0.25mg/(kg.d)〕组、TLSFJM〔10U/(kg.d)〕组和FK506〔0.25mg/(kg.d)〕+TLSFJM〔10U/(kg.d)〕组。FK506和TLSFJM分别以肌肉或腹腔注射方式给药。在不同时间段分别观察各组动物体重、生存时间及肝、肾功能,组织病理学检查排斥反应发生情况。结果TLSFJM应用7d,对移植大鼠肝、肾功能无损害。TLSFJM+小剂量FK506不但避免了大剂量FK506对肝功能的损害,而且显著延长了受体的生存时间。但单独应用TLSFJM仍有一定程度排斥反应出现,不能明显延长受体的生存时间。结论TLSFJM作为一种有效的移植免疫抑制因子,联合小剂量FK506应用能延长宿主和移植肠的生存时间,延缓排斥反应的发生,减轻排斥反应的强度,避免大剂量FK506治疗带来的并发症。TLSFJM有望成为一种新型、高效、低毒的免疫抑制剂。

Objective To investigate the inhibitory effect and its mechanisms of TLSF JM （JM acute T leukemia cell line derived suppressor factor） on allograft rejection of small bowel transplantation in rat, and to compare the effects and complications of TLSF JM with those of FK506. Methods One hundred male Brown Norway （BN） rats and 100 Lewis （LEW） rats were treated as donors and recipients of small bowel transplantation, respectively. Then they were divided into five groups according to the dose of administration of TLSF JMand/or FK506.. small bowel transplantation group （SBT group）; large dose of FK506 [0.5 mg/（kg · d）] group; small dose of FK506 [0.25 mg/（kg· d）] group; TLSFjM [10 U/（kg · d）] group; TLSFjM [10 U/（kg· d）] associated with small dose of FK506 [0.25 mg/（kg · d）3 group. FK506 and TLSF JM were administered through intramuscular or intraperitoneal injection, respectively. Survival time, body weight, hepatic and renal function and histopathology of recipients in each group were observed. Results TLSF JM took no damage effect on the recipients＇ renal and hepatic functions 7 days after administration. When TLSF JM was administrated associated with small dose of FK506 in small bowel transplantation, it could not only effectively suppress rejection reaction, extend recipient＇s survival time, but also decreased the dosage of FK506 and prevented the side effects. But TLSF JM may not be used as immunosuppressive agent alone for the prevention and treatment of rejection in rat small bowel transplantation because the rejection still existed. Conclusion As an effective immunosuppression agent, TLSF JM associated with small dose of FK506 can prolong the survival time of both recipients and grafting small bowel, relieve intensity of rejection, and prevent the side effects when high dosage FK506 is administrated. TLSF JM may be used as a high-efficiency, low-toxicity immunosuppresive agent in small bowel transplantation.