他克莫司局部用药在异体复合组织移植中的应用研究

Topical administration of tacrolimus prolong the survival of the epigastric flap allografts in rats

目的:探索在异体复合组织移植后局部应用他克莫司预防免疫排斥的效果。方法:以Lewis鼠和Brown Norway鼠为实验动物,进行腹部游离皮瓣异体移植,其中Brown Norway大鼠为供体,Lewis大鼠为受体。实验分为3组:全身用药组(A组),局部用药组(B组)和空白对照组(C组),在移植术后10天内均先给予腹腔注射环胞素A(20mg/kg/天),此后A组继续全身用药,而B组和C组仅在皮瓣局部分别给予他克莫司涂抹剂或赋形剂氮酮(均为2mg/kg/天)。通过观察皮瓣存活时间,皮瓣组织病理学检查,他克莫司血药浓度和局部组织药物浓度以及全身IL-2的变化,探讨局部应用他克莫司的效果。结果:三组皮瓣平均存活时间分别为:>100天(A组),25天(B组)及17天(C组),〉通过对比和统计学分析可以看出,局部用药可以延长异体皮瓣的存活时间,但是仅靠局部用药仍无法避免排斥反应的发生。结论:局部用药可以延长异体皮瓣的存活时间,但是仅靠局部用药仍无法避免排斥反应的发生。对于异体复合组织移植,局部应用他克莫司可以延长皮瓣的存活时间,但存活时间有限;但是在全身用药的基础上,局部用药可以降低全身用药的剂量,而保证异体皮瓣长期存活。因此,为了减少全身用药所带来的毒副作用,对于异体复合组织移植来说,局部应用他克莫司是一种可行的方案。

Objective To study the effect of topical tacrolimus （FK506）on the survival of composite tissue allografts by the epigastric flap allografts in rats. Methods In our study, lewis rats were used as recipients and Brown Norway rats were used as donor. We harvest the lower abdominal flaps of Brown Norway rats based in the femoral artery and vein, then the allograts were orthotopicly transplanted to Lewis rats. 30 couples of rats were divided in 3 groups： group A, systemic CsA; Group B, systemic CsA for 10 days prior to topical tacrolimus; Group C, systemic CsA for 10 days prior to blank control group with topical Azone. Postoperative, we compared the survival time of the composite-tissue flap and their histologic outcomes. We also measured the systemic CsA levels, tissue FK506 levels and systemic FK506 levels, and the level of IL-2 to verified the practicability of topical tacrolimus. Results The survival time was 〉100d in Group A, 25d in Group B and 17d in Group C, respectively. Topical therapy with tacrolimus can prolong the survival time of the allograft temporarily. Conclusion Topical administration of tacrolimus prolong the survival of the epigastric flap allografts in rats.