环孢菌素A预处理对大鼠移植心脏缺血再灌注时心肌TNFα、MPO的影响

Effects of cyclosporin A pretreatment on expressions of tumor necrosis factorα and myeloperoxidase and in rat cardiac allografts during ischemia-reperfusion

目的 :探讨移植心脏再灌注时心肌肿瘤坏死因子α(TNFα)表达、髓过氧化物酶 (MPO)水平的变化及环孢菌素A(CsA)预处理对移植心脏再灌注损伤 (I/R)的影响。方法 :将 84只雄性Wistar大鼠随机分为对照组 (C组 )和实验组 (E组 )。 2组均分为 0h、3h、6h、2 4h 4个时间点。其中每组 0h作为缺血再灌注前对照 ,均为 6只。而 2组其他 3个时间点则为供、受体动物各 6只。 2组的 3h、6h、2 4h 3个时间点动物移植心缺血时间约为 5 0min。E组供、受体鼠术前 1h尾静脉注射CsA(10mg/kg)。分别于再灌注 0h、3h、6h、2 4h取移植心测定心肌TNFα、MPO水平及心肌含水量的变化。结果 :①C组移植心再灌注后心肌TNFα明显升高 ,于再灌注 3h最显著 ,且明显高于 0h(P <0 .0 1)。E组再灌注 3h、6h、2 4h心肌TNFα水平均明显低于同期C组 (P均 <0 .0 5 )。②C组再灌注后心肌MPO含量、心肌含水量逐渐升高 ,于 6h最明显 ,与 0h相比 ,P <0 .0 1。E组再灌注 3h、6h、2 4h心肌MPO含量、心肌含水量明显低于同期C组 ,P均 <0 .0 5。结论 :①心脏移植再灌注后心肌TNFα、MPO明显升高 ,且参与了心肌再灌注损伤。②供、受体应用CsA预处理可以抑制TNFα的表达 ,降低MPO水平 ,减轻心肌水肿 。

Aim:To investigate effects of cyclosporin A (CsA) pretreatment on the expressions of tumor necrosis factorα(TNFα) and myeloperoxidase(MPO) in rat cardiac allografts during the stage of ischemia reperfusion (I/R).Methods:Eighty four male Wistar rats were allocated into 2 groups at random: control group(C) and experimental group (E).Both groups were allocated into 4 time points(0 h, 3 h, 6 h,and 24 h after ischemia and reperfusion)groups. 0 h point group( n =6)acted as the control before I/R. For the rest 3 time point groups, both donors and recipients had 6 animals. The ischemic time was about 50 min for each subgroups. A single dose of CsA (10mg/kg intravenously) for group E and normal saline for control groups was administered to both the donor and the recipient rats 1h before heart explantation and heart transplantation respectively. At time points of 0 h, 3 h, 6 h, and 24 h, the cardiac allografts were removed to determine TNFα, MPO, and percentage of myocardial water. Results:In group C, levels of TNFα increased gradually after reperfusion and reached peak at 3h. There was a significant discrimination between 3 h and 0 h in the control group ( P <0.01). The levels of TNFα in group E were significantly lower than those group C at time points of 3 h, 6 h, and 24 h ( P < 0.05);MPO and percentage of myocardial water was significantly higher at 6 h than that at 0 h in group C ( P < 0.01 ), and there was a significant discrimination between groups E and C at 3 h, 6 h, and 24 h ( P <0.05, P <0.01, P < 0.05).Conclusions:TNFα and MPO upregulation participates in the reperfusion injury in cardiac allografts; CsA pretreatment is effective in preventing reperfusion injury in rat cardiac transplant models.