异基因大鼠心脏移植慢性排斥模型的建立

Lmproved Technique for Chronic Graft Vascular Disease in a Rat Cardiac Allograft Model

目的:探讨快速建立异基因大鼠心脏移植慢性排斥动物模型的方法。方法:以Lewis大鼠为供体,F344大鼠为受体,建立心脏移植模型共54只。随机分为3组,即空白对照组、CsA2mg·kg-1组和CsA6mg·kg-1组(每组18只)。空白对照组术后每天腹腔注射0.9%氯化钠溶液,试验组腹腔注射CsA2mg·kg-1或CsA6mg·kg-1,连续10d。术后20、40和60d时分批处死,取移植心脏行病理检查,对冠脉血管重塑和单核细胞浸润情况进行评分。结果:(1)对照组有7(39%)只大鼠出现移植心停跳,CsA6mg·kg-1组有2(11%)只大鼠带心死亡。(2)术后40d各组都出现典型的冠脉内膜增生病变,术后60d病变更加明显。(3)各时段CsA组冠脉内膜增生程度与对照组相比无显著差异。单核细胞浸润程度较对照组减轻,术后20d有显著差异(P<0.05)。结论:选用近交系的Lewis和F344大鼠建立心脏移植模型,移植后给予短程、小剂量CsA(2mg·kg-1)干预,术后40d可以获得较为稳定的慢性排斥动物模型。

Objective： To establish an optimal model for the study of cardiac allograft vasculopathy（CAV） after heterotopic heart transplantation in rats. Methods： Fifty-four heterotopic heart transplantations had been performed between Lewis （recipients） and F344 rats （donors）. The recipients had been divided into control group, cyclosporine A （CsA） 2 mg· kg^-1 group and CsA 6 mg· kg^-1 group randomly. The vehicle and CsA （2 mg · kg^-1 or 6 mg· kg^-1） were injected respectively in different groups from 0^th day to 9th day after operation. Six allografts were removed and examined histologically on 20th day, 40^th day and 60^th day after transplantation in each group. CAV score had been evaluated. Results： （1）Seven （39%） allografts lost in control group and two（11 %） rats died in CsA 6mg/kg group. （2）Allografts presented typical CAV in all groups on 40^th day and more serious on 60th day after transplantation. （3）There was no difference between control group and CsA treated groups in graft vascular remodeling. The severity of mononuclear cell infiltration was significantly different between CsA treated groups and control group （P〈0. 05） on 20^th day after transplantation. Conclusion：With a 10-days 2 mg · kg^-1 CsA treatment, the allograft presented typical CAV on 40^th day after transplantation between F344 （recipient） and Lewis （donor）.