目的探讨异基因大鼠皮瓣移植模型中雷帕霉素阶梯用药方案的疗效。方法建立近交系大鼠下腹部皮瓣移植模型。Ⅰ组(n=5)不予免疫抑制剂;Ⅱ组(n=5)给予雷帕霉素2mg·kg-1·d-1;Ⅲ组(n=5)给予雷帕霉素4mg·kg-1·d-1;Ⅳ组(n=8)术后第1~2周给予雷帕霉素4mg·kg-1·d-1,第3周改为2mg·kg-1·d-1,第4周后减量至1mg·kg-1·d-1。3组给药时间持续至术后60d或移植皮瓣死亡为止。大体观察各组移植皮瓣排斥反应发生的时间。分别于术后7、15、30d取移植皮瓣皮肤组织(每个时间点每组3只)行HE染色,观察病理学变化。结果Ⅲ组5例全部存活至术后60d,Ⅳ组7例存活至术后60d,而Ⅱ组移植皮瓣在术后60d前全部发生排斥反应,Ⅳ组与Ⅱ组比较移植皮瓣存活率差异有统计学意义(P〈0.05),与Ⅲ组比较差异无统计学意义(P〉0.05)。根据Banff07标准评分,术后7d时Ⅰ组为3级,其余各组为0级;术后15d时Ⅱ组为2级,Ⅲ、Ⅳ组为0级;术后30d时Ⅳ组中1例为4级,其余存活移植皮瓣为0级。结论本实验证实雷帕霉素阶梯用药与大剂量持续给药有相同的抑制排斥反应效果。
Objective To establish a tapering immunosupression protocol with rapamycin monotherapy in a rat free flap allotransplantation model.Methods Vascularized epigastric flaps were transplanted from Brown Norway to Lewis rats.No immunosuppressant was given to group Ⅰ(n=5).Rapamycin of 2 mg·kg-1·d-1was given intraperitoneally to group Ⅱ and 4 mg·kg-1·d-1to Group Ⅲ after allotransplantation.In group Ⅳ,rapamycin was given at the dose of 4 mg·kg-1·d-1during the first two weeks after operation,at the dose of 2 mg·kg-1·d-1during the third week,and at the dose of 1 mg·kg-1·d-1from the fourth week to the end.Rejection was evaluated by gross anatomic appearance.Histological examination was performed on the postoperative day 7,15,and 30.Results The number of allografts survivedfor 60 days after operation was 0,5,and 7 in group Ⅱ,Ⅲ,and Ⅳ,respectively,with a significant difference between group Ⅱ and Ⅳ(P0.05).The difference between group Ⅳ and group Ⅲ was not significant(P0.05).According to Banff classification,group Ⅰ was classified to grade 3 and other groups were classified to grade 0 on the postoperative day 7;group Ⅱ was classified to grade 2 and other groups were classified to grade 0 on the postoperative day 15;group Ⅲ and Ⅳ were classified to grade 0 except for one case in group Ⅳ was classified to grade 4.Conclusion This study indicated that tapering rapamycin monotherapy protocol had the equivalent efficacy to consistent high-dose rapamycin monotherapy.