半胱氨酰天冬氨酸特异性蛋白酶-3抑制剂对体外循环时兔心肌的保护作用

The protection of the Caspase-3 inhibitor on cardiopulmonary bypass-induced cardiac function injury in the rabbit model

目的 观察半胱氨酰天冬氨酸特异性蛋白酶（Caspase）-3抑制剂对体外循环时心肌的保护作用.方法 清洁健康新西兰大白兔（体质量为2.0 ～2.5 kg,雌雄不拘）30只,随机分为对照组和Caspase-3抑制剂Ac-DEVD-CHO组（术前0.5h经股静脉给予Ac-DEVD-CHO 5 ml/kg,术中停止体外循环后再经股静脉给予5 ml/kg）.分别在术前、体外循环转流中和转流后检测各组肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白（cTnⅠ）、Caspase-3活性和髓过氧化物酶（MPO）活性变化.结果 Caspase-3抑制剂组与对照组比较,血cTnⅠ水平（g/L） （0.03 ±0.02、0.03±0.06、0.08 ±0.04、0.09±0.02比0.03±0.01、0.06±0.03、0.12 ±0.05、0.17±0.07）和CK-MB浓度（U/L）均明显降低（111.39±0.03、134.26 ±3.45、342.49±5.35、501.25±8.31比100.41 ±0.02、435.21±6.38、987.32±25.17、1 264.53±22.08）,Caspase-3活性（z/pmol/h/mg）受到明显抑制（0.03±0.01、0.09±0.02、0.18 ±0.03、0.39±0.02比0.02 ±0.01、0.16±0.05、0.72 ±0.04、0.87 ±0.06）,MPO活性显著降低（μg/L） （0.33 ±0.02、0.53 ±0.03、0.67±0.03、0.88 ±0.05比0.33±0.01、0.96 ±0.04、1.12±0.03、2.17 ±0.02）,差异有统计学意义（F=36.10 ～574.13,P＜0.05）.结论 Caspase-3抑制剂对体外循环时心功能损伤起到一定的保护作用.

Objective To investigate the protection of the Caspase-3 inhibitor （Ac-DEVD-CHO） on cardiopulmonary bypass （CPB）-induced ischemia reperfusion injury in the rabbit model.Methods Rabbits were divided into two groups：control （C） group and Ac-DEVD-CHO （A） group.In the C and A groups,animals underwent CPB at a flow rate of 50-70 ml/kg per min,Ac-DEVD-CHO （5 ml/kg） was administered to the A group rabbits by intravenous injection 30 min before operation and Ac-DEVD-CHO （5 ml/kg） was administered by intravenous infusion while reperfusion being done.The myeloperoxidase （MPO） and Caspase-3 activity,the blood creatine kinase isoenzyme MB （CK-MB） and cardiac troponin Ⅰ （cTnⅠ） in each group were detected.Results A comparison between A group and C group showed that for treated group,the levels of CK-MB （U/L） （111.39 ± 0.03,134.26 ± 3.45,342.49 ± 5.35,501.25 ±8.31 vs.100.41 ± 0.02,435.21 ± 6.38,987.32 ± 25.17,1 264.53 ± 22.08） and cTnⅠ （g/L） （0.03 ±0.02,0.03±0.06,0.08±0.04,0.09±0.02 vs.0.03 ±0.01,0.06±0.03,0.12±0.05,0.17±0.07）were both decreased,the activity of Caspase-3 （z/pmol/h/mg） （0.03 ±0.01,0.09 ±0.02,0.18 ±0.03,0.39±0.02 vs.0.02±0.01,0.16 ±0.05,0.72 ±0.04,0.87 ±0.06） and MPO（μg/L） （0.33±0.02,0.53 ±0.03,0.67 ±0.03,0.88 ±0.05 vs.0.33 ± 0.01,0.96 ±0.04,1.12 ±0.03,2.17 ±0.02） were inhibited （F =36.10-574.13,P 〈 0.05）.The differences of the above items were of statistically significant.Conclusion Ac-DEVD-CHO inhibited the changes in the MPO and Caspase-3 activity and decreased the blood CK-MB and cTnⅠ in simulated extracorporeal circulation.This study suggests that Ac-DEVD-CHO could be feasible therapeutic strategy to protect the cardiac function injury in patients undergoing cardiopulmonary bypass.