环孢素聚乳酸微球在同种异体气管移植中的应用

Cyclosporin A polylactic acid microspheres in tracheal allotransplantation

背景:前期实验已获得了最优的环孢素聚乳酸微球制备工艺,且证实微球具有明显的缓释性能,无明显毒、副作用。目的:观察同种异体原位气管移植后,局部置入环孢素聚乳酸微球对免疫排斥的抑制作用。设计、时间及地点:随机对照动物实验,于2007-02/04在解放军第二五二医院医院动物实验中心完成。材料:选取SD大鼠60只,按体质量配对后行同种异体气管原位移植。移植后按随机数字表法分为3组,即空白对照组、环孢素注射组及环孢素聚乳酸微球局部应用组,每组10只。方法:空白对照组不做特殊处理;环孢素注射组于气管原位移植后给予环孢素肌肉注射;环孢素聚乳酸微球局部应用组于气管原位移植后分别将10,30mg环孢素聚乳酸微球埋植于气管周围肌肉层内、外。主要观察指标:移植后4周麻醉后处死动物,对移植气管标本进行大体及病理学评估,计算上皮积分、淋巴细胞计数以及无核软骨细胞/全部软骨细胞比值等指标,并进行组间比较。结果:①环孢素注射组、环孢素聚乳酸微球局部应用组大鼠全部存活至预杀期,空白对照组大鼠死亡1只。②移植后4周环孢素注射组、环孢素聚乳酸微球局部应用组的上皮积分均高于空白对照组(P<0.01);环孢素聚乳酸微球局部应用组高于环孢素注射组(P<0.01)。③移植后4周环孢素注射组、环孢素聚乳酸微球局部应用组的淋巴细胞计数均低于空白对照组(P<0.05,0.01);环孢素聚乳酸微球局部应用组低于环孢素注射组(P<0.05)。④移植后4周环孢素注射组、环孢素聚乳酸微球局部应用组无核软骨细胞与所有软骨细胞比值均低于空白对照组(P<0.05)。结论:同种异体气管原位移植后局部置入环孢素聚乳酸微球可以有效降低免疫排斥反应,对移植体的保护作用优于肌肉注射环孢素。

BACKGROUND： In previous trials, optimal Cyclosporin A polylactic acid microsphere （CyA-PLA-MS） technique has developed, and the microsphere is slow-released with rio toxic or side effect. OBJECTIVE： To observe the immune suppression of locally administered CyA-PLA-MS for tracheal allotransplantation in rats. DESIGN, TIME AND SETTING： Randomized controlled animal trial was performed at the animal experimental center of the 252 Hospital of Chinese PLA from February to April 2007. MATERIALS： Sixty SD rats were selected and underwent tracheal allotransplantation following body mass matching. The rats were randomly divided into 3 groups （n= 10） following transplantation： black control, Cyclosporin A and CyA-PLA-MS groups. METHODS： The black group was not given any specific treatment; Cyclosporin A group was intramuscularly injected with Cyclosporin A following transplantation; 10 and 30 mg CyA-PLA-MS was implanted into inner and outer muscle layers surrounding the trachea following transplantation. MAIN OUTCOME MEASURES： The rats were sacrificed 4 weeks post-operation. Gross and pathological evaluations of tracheal graft were performed; epithelium scores, lymphocyte count and ratio of acaryotic chondrocyte and entire chondrocyte were calculated and compared among groups. RESULTS： Only one rat in the blank control group died. The epithelium score of Cyclosporin A and CyA-PLA-MS groups was significantly greater than the control group （P 〈 0.01）, and CyA-PLA-MS group was greater than Cyclosporin A group （P 〈 0.01）. The number of lymphocyte of Cyclosporin A and CyA-PLA-MS groups was significantly smaller than the control group （P 〈 0.05, 0.01）, and CyA-PLA-MS group was smaller than Cyclosporin A group （P 〈 0.05）. The ratio of nucleated chondrocyte showed statistical differences between Cyclosporin A and CyA-PLA-MS groups and control group （P 〈 0.05）. CONCLUSION： Locally administered CyA-PLA-MS exhibits markedly immunosuppressive effect following orthotopic tracheal transplantations in rats, and the protective effect is superior over intramuscular injection of Cyclosporin A.