环孢素A在鼠喉移植中的抗免疫排斥作用

Immunosuppression Effect of CsA in Laryngeal Allotransplantation

【目的】研究环孢素A(CsA)在同种异体鼠喉移植中的抗免疫排斥效应,探索同种异体鼠喉移植的抗免疫排斥方案。【方法】采用已建立的改良模型进行鼠喉移植,以Wistar大白鼠为供体鼠,SD大白鼠为受体鼠,按照术后CsA用量分为0 mg/kg·d(对照组)、5 mg/kg·d(A组)、7.5 mg/kg·d(B组)、10 mg/kg·d(C组)、15 mg/kg·d(D组)、CsA5 mg/kg·d+甲强龙5 mg/kg(E组)共6组,每组10对;术后21 d解剖受体鼠,观察移植喉的大体形态变化和镜下结构;比较各剂量组可评价移植喉的免疫分级均数。【结果】每组受体鼠最终存活10只,A、B、C、D、E组和对照组的可评价移植喉数分别为3、6、4、2、6、2个,移植喉梗死和严重感染数分别为3、2、2、3、1、2个和1、2、3、5、2、2个,可评价移植喉平均免疫排斥分级分别为3.67、2.5、3.20、3.00、2.29、3.67。【结论】CsA可以对同种异体鼠喉移植产生免疫抑制,降低移植喉的免疫排斥分级;单用CsA的最佳剂量为7.5 mg/kg·d;联合使用甲强龙5.0 mg/kg·d可降低CsA使用剂量至5.0 mg/kg·d而不增加移植喉的免疫排斥分级和继发感染的可能性。

[Objective] The study was designed to explore the immunosuppression effect of CsA in laryngeal allotransplantation, the ultimate purpose of which was to establish an antiimmunorejection protocol for laryngeal allograft. [Methods] The newly established modified laryngeal transplantation model was used in the research, in which Wistar served as donor and SD served as recipient. The intramuscular injected CsA was administered at dose of 0, 5, 7.5, 10, 15, and CsA 5 mg/kg.d ＋ Methylprednisolone 5 mg/kg in the six groups, respectively. The recipients were sacrificed 21 days after transplantation for gross and microscopic observation. Infarction and severe infection were considered as transplantation failure and the allograft unevaluable. Average immunorejection grade was compared among different groups. [ Results] Ten recipients survived in each group. Evaluable transplanted larynes in group A, B, C, D, E, and controlled group were 3, 6, 4, 2, 6, and 2, respectively, while infarction occurred in 3, 2, 2, 3, 1, and 2 allografl, severe inflammation in 1, 2 3, 5, 2, and 2 allograft, respectively. Average rejection grades of the evaluable allograft in the aforementioned group were 3.67, 2.5, 3.20, 3.00, 2.29, and 3.67, respectively. [Conclusion] CsA reduce immunorejection grade of the allografl. The optimal dose of single CsA was 7.5 mg/kg.d in our trial. Combined with Methylprednisolone in a dose of 5.0mg/kg.d, the dosage of CsA could be reduced to 5.0 mg/kg.d without increased rejection grade of the allograft or increased potential secondary infection of the allografl.