局部应用环孢素A以延长同种移植皮片存活的实验研究

PROLONGATION OF SKIN ALLOGRAFT SURVIVAL BY TOPICAL USE OF CYC-LOSPORINE A (CsA)

为减低环孢素(CsA)的毒性作用,试以局部使用CsA于大鼠同种皮移植(BUF→LEW),使平均存活期(MST)自9.8±0.4天延长至12.0±0.3天。血液CsA浓度仅为94±18ng/ml。将两块ACI皮片同植于同一只LEW大鼠,局部用药一侧MST为12.1±0.7天,明显长于对照侧的9.1±0.3天,且二者均比单植1块皮的对照组的MST6.5±0.2天有明显延长。说明局部应用CsA,其主要作用在局部,有明显抑制免疫排异作用,但也有一定的全身性作用。

A long course of systemic treatment with CsA in therapeutic dose to prolong skin allografts may produce severe toxic effects,therefore it is not acceptable for severe burn patients.Prior studies by one of us have reported that topical treatment with CsA will prolong the life of allografts.During the period of treatment,however,blood CsA levels were detected in high concentrations,similar to systemic use.The question occurs whether the immunosuppressive effect of topically applied CsA was due to local or systemic action.Two experiments were carried out.First,two skin grafts of ACI (RT1) ratswere transplanted on both sides of the back of same LEW (RT1) rat (n=56).The bandage was kept on for the first 5 postoperative days.One graft was treated topically daily with CsA 7.5mg/day in olive oil until rejection.At the same time,the other side was treated with olive oil alone as control.,The mean survival time (MST) was 12.38±0.70 and 9.14±0.33 d.,respectively,p<0.001 by Wilco-xon's test.In the second experiment,BUF (RT1) rat skin was transplanted on LEW rats.CsA or olive oil (as control)was topically applied daily,and the grafts were bandaged until rejection to prevent the animal from ingesting CsA.The blood CsA level was 04.3±18.2ng/ml on the 7th postoperative day.The MST was 12.0±0.30 and 9.88±0.40 days,respectively.These findings indicate that there is both a systemic and local immunosuppressive effect of topical cyclosporine A.