FTY720对大鼠同种异体异位心脏移植物缺血-再灌注损伤的影响

Effects of FTY720 on ischemia-reperfusion injury of rat cardiac allografts

目的:观察FTY720对同种异体异位心脏移植物缺血-再灌注损伤的影响并探讨其相关机制。方法:利用Cuff技术建立颈部异位心脏移植模型。FTY720组(n=6)受体鼠自术前3 d开始至手术当日管饲FTY720,剂量为3 mg/kg;对照组(n=6)受体鼠自术前3 d开始至手术当日管饲生理盐水,剂量为1 mL/kg。于移植后8 h切取移植心脏,电镜下观察心肌组织超微结构变化;TUNEL法测细胞凋亡,计算凋亡指数;测定心肌组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和髓过氧化物酶(MPO)活性。结果:移植后8 h,FTY720组心肌细胞形态基本正常,仅轻度水肿,间质水肿和炎性细胞浸润不明显;电镜超微结构显示心肌肌丝排列整齐,肌原纤维间轻度水肿,线粒体饱满,嵴密,水肿不明显,无明显的肌丝断裂现象。FTY720组只有少量心肌细胞凋亡,凋亡指数为(9.20±1.12),对照组心肌细胞凋亡明显,凋亡指数为(16.10±1.65)(t=8.475,P<0.001)。FTY720组SOD活性较对照组升高[(51.03±5.54)mmol/gvs.(28.39±2.38)mmol/g],而MDA含量[(10.90±1.93)U/gvs.(16.27±1.36)U/g]和MPO活性[(4.38±1.43)mU/gvs.(9.26±1.41)mU/g]下降(t分别为9.197、5.571和5.592,P均<0.001)。结论:FTY720能减轻大鼠移植心脏缺血-再灌注损伤。

Aim ： To study the effects of FTY720 on ischemia-reperfusion injury of rat cardiac allografts. Methods：The model of rat heterotopic heart transplantation was established with Cuff technique. The recipient rats of the FTY720-treated group （n = 6） was administered with FTY720 orally at a dosage of 3 mg/kg for 3 days before grafting operation,and the control group was administered with normal saline at a dosage of 3 mL/kg. All recipients were sacrificed and the donor hearts were removed at 8 hours after transplantation. The ultrastructure of the graft tissues was observed under electron mi- croscope. Apoptosis index （AI） in grafts was determined by TUNEL. Grafts＇ SOD activity, MDA content, and MPO activ- ity were measured. Results： At 8 hours after transplantation in FTY720-treated group, there were less cellular swelling, less inflammatory cell infiltration and less mitoehondrial oedema of cadiocyte. Compared with control group,the cell apopto- sis in FTY720-treated group decreased [AI：（9.20 ±1.12） vs. （16. 10 ± 1.65）,t =8.475,P〈0.001）],SOD activity [（51.03 ±5. 54） mmol/g vs. （28. 39 ±2. 38） mmol/g] was higher, and MDA content[（10.90 ± 1.93） U/g vs. （16.27 ±1.36） U/g] and MPO activity [（4.38 ± 1.43） mU/g vs. （9.26 ± 1.41） mU/g] were lower（t =9. 197, 5. 571, and 5. 592 ,P 〈 0. 001 ）. Conclusion： FTY720 could ameliorate the myocardial ischemia-reperfusion injury in rat heart transplantation