摘要
【目的】研究供心长时间低温保存后缺血再灌注损伤导致的心肌细胞凋亡,明确抗调亡因子在心脏移植供心缺血再灌注损伤中的保护作用,为心脏保护液药物研究提供帮助。【方法】24只实验SD大鼠分2组,建立大鼠心脏异位移植模型,在围手术期、供心保存过程中使用天冬氨酸特异性半胱氨酸蛋白酶3抑制剂(Ac-DEVD-CHO)干预,使用HTK保存液低温保存供心9h,监测模型前后,检测凋亡相关因子和病理学指标。【结果】在异位移植开放后60min,①实验组的心率恢复率[(71.9±6.9)%]高于对照组[(59.6±10.5)%;P<0.05]。②实验组的心肌Caspase-3活性(0.695±0.040)低于对照组(3.438±0.035;P<0.01)。③实验组的心肌梗死面积(5.29±2.33)低于对照组(22.10±3.00;P<0.01)。④实验组的凋亡指数(5.09±2.31)低于对照组(13.4±2.5;P<0.01)。⑤心肌组织HE染色:对照组的心肌组织损伤较实验组严重。【结论】①供心长时间低温保存再灌注后细胞出现明显凋亡,心肌细胞凋亡是心脏移植供心长时间保存缺血再灌注后心功能下降的主要机制之一。②使用半胱天冬酶抑制剂能明显抑制心肌细胞凋亡,减轻供心缺血再灌注损伤,改善供心心功能,是提高供心保存时效的良好方法。③半胱天冬酶抑制剂Ac-DEVD-CHO对供心保存的时-效和量-效关系仍有待进一步探讨。
[Objective] TO study the apoptosis after long time of heart preservation, and the barrier of caspase （Ac-DEVD- CHO） in prolonged heart transplantation. To improve the techniques on the preservation of donor heart. [Methods] Donor rat hearts were subjected to group A （non-Ac-DEVD-CHO-treated）, group B （Ac-DEVD-CHO-treated） of hypothermic storage, after 9 hours of heart preservation, then performed heterotopic heart transplantation, followed by 60 min of normothermic reperfusion （n = 6 in each group）. [Results] After 60 min reperfusion, compared with group A, （1） a significant improvement in the percent recovery of HR was observed in group B （P 〈 0.05） ; （2）Caspase-3 activity was decreased in group B （P 〈 0.01 ） ; （3）an apparent decline in the expression of infarct area was observed in group B （P 〈 0.01）; （4）an apparent decline in the expression of TUNEL- positive cardiomyocyte was observed in group B （P 〈 0.01）; （5） Group B shows the least disease. [Conclusion] （1） After preservation and reperfusion, cardiomyocyte apoptosis was observe evidently, which led to irreversible heart dysfunction. （2） The administration of caspase-3 inhibition after repeffusion attenuates ischemia-reperfusion injury by suppressing apoptosis in heart transplantation. Furthermore, the use of caspase inhibition was investigated as a strategy for the preservation donor heart in transplantation. （3）The relationship of dose-response and time-effect is still unknown.
出处
《中山大学学报（医学科学版）》
CAS
CSCD
北大核心
2009年第4期390-394,共5页
Journal of Sun Yat-Sen University:Medical Sciences
基金
广东省自然科学基金(7001109)
关键词
凋亡
供心
缺血-再灌注损伤
apoptosis
donor heart
ischemie-reprefusion injury
