Application of Microsphere Including Taclorimus-FK506 to Immunosuppression for Small Bowel Transplantation

尽管免疫抑制技术有所改进，排斥反应仍然是肠移植成功的主要障碍。需要一种效果更好、副作用更小的新型免疫抑制剂。将新型他克莫司（FK506）生物可降解微球应用于猪全小肠移植实验，通过混合淋巴细胞反应证实供体和受体之间存在异体。移植后每3天进行一次内镜组织活检，每天进行他克莫司（TAC）血药水平检测。研究组包括TAC-0.5mg/kg、TAC-0.2mg/kg、含TAC微球（MS-TAC）0.5mg/kg、MS-TAC0.1mg/kg、MS-TAC0.4mg/kg和MS-TAC0.02mg/kg。生存期分别为9.7、11.0、12。7. 5. 分别为28.6 ~ 9.5天。TAC谷水平分别为27.9、10.9、60.6、40.3、24.6、10.5、9.5 ng/ml。所有仅服用TAC的动物都有排斥反应，服用0.5mg/kg TAC的动物有40%发生感染。MS-TAC0.1、0.5、1.0均无排斥反应，但均有感染。MS-TAC0.04无排斥反应和感染。半数MS-TAC0.02患者有排斥反应，但无感染。MS-TAC0.04在该模型中生存期更长，副作用更小。MS-TAC在小肠移植中具有良好的免疫抑制作用，副作用小。

Rejection remains a major barrier to successful bowel transplantation, despite improved immunosuppressive techniques. New immunosuppressant which has more effect and less side effect is needed. New biodegeneradable microsphere containing Tacrolimus (FK506) was applied to experimental porcine whole small bowel transplantation in which allogenesity between donors and recipients were confirmed by mixed lymphocyte reaction. After transplantation, endoscopic biopsy for histology every 3 days and Tacrolimus (TAC) blood level test daily were performed. Study groups consisted of TAC-0.5mg/kg, TAC-0.2mg/kg, microsphere containing TAC(MS-TAC)0.5mg/kg, MS-TAC0.1mg/kg, MS-TAC0.4mg/kg and MS-TAC0.02mg/kg. Survival period was 9.7, 11.0, 12. 7. 5. 28.6 9.5 days, respectively. TAC trough level was 27.9, 10.9, 60.6, 40.3, 24.6, 10.5, 9.5 ng/ml, respectively. All animals with merely TAC had rejection and 40% of TAC0.5mg/kg had infection. All of MS-TAC0.1, 0.5, 1.0 had no rejection but had infection. Non of MS-TAC0.04 had rejection and infection. Half of MS-TAC0.02 had rejection but not infection. MS-TAC0.04 achieved longer survival and less side effects in this model. MS-TAC has a great potency in immunosuppression with less side effects for small bowel transplantation.