血红素氧合酶-1对移植的异种心脏的保护作用

目的探讨血红素氧合酶-1(HO-1)对移植的异种心脏的保护作用及其可能机制。方法应用NI H小鼠到Wistar大鼠颈部异位心脏移植模型,术前对供者分别用HO-1的诱导剂CoPP或HO-1的阻滞剂ZnPP进行处理,术后受者相应接受CoPP或ZnPP处理,部分受者同时接受环孢素A(CsA)处理,并设空白对照组和单用CsA组。分别用免疫组化、逆转录聚合酶链反应、Westernblot蛋白印迹杂交等检测移植心组织中HO-1、HO-1mRNA、凋亡蛋白酶-3以及信号传导与转录因子-3(STAT-3)的表达,测定心肌组织中HO-1的活性,采用原位末端标记法检测心肌细胞凋亡情况,比较不同处理因素之间的差异。结果单一接受CoPP者(CoPP组)移植心脏存活时间长于空白对照组及单一接受ZnPP者(P<0.01),但短于同时接受CoPP和CsA处理者(CoPP CsA组,P<0.01);CoPP组及CoPP CsA组HO-1、HO-1mRNA的表达及HO-1的活性均高于其余各组(P<0.01),其心肌细胞凋亡数和凋亡蛋白酶-3低于其余各组(P<0.05),而STAT-3高于其余各组(P<0.01)。结论CoPP诱导产生的HO-1可延长NI H小鼠到Wistar大鼠异种移植心脏的存活时间,该作用可能与STAT-3激活、凋亡蛋白酶-3受抑制而导致心肌细胞凋亡发生率下降有关。

Protective effect of heme oxygenase-1 for xeno-heart transplantation

Objective To investigate the protective effect of heme oxygenase-1 for xeno-heart transplantation and the possible mechanism.Methods Cobalt protoporphyrin (CoPP), HO-1 inducer, and zinc protoporphyrin (ZnPP), HO-1 inhibitor, were used to intervene donors and recipients on the model of NIH-Wistar cardiac transplants respectively and simultaneously some of recipients were treated with immunesuppressor cyclosporine A (CsA), and control group and CsA treated group were set up respectively. The expression of HO-1 protein, HO-1 mRNA, caspase-3 and STAT-3 in transplanted heart tissue was detected by immunohistochemistry, RT-PCR and Western Blot. At the same time, HO-1 enzymatic activity was examined in heart tissue, and the cardiac cell apoptosis was examined by means of TUNEL. The differences among various factors were compared.Results The survival time of cardiac transplants in CoPP group was longer than that in control and ZnPP groups (P< 0.01), and shorter than that in group CoPP CsA (P< 0.01). The expression of HO-1 mRNA and protein and enzymatic activity in groups CoPP and CoPP CsA were higher than those in other groups (P< 0.01). The cardiac apoptotic number and caspase-3 in the same two groups were lower than those in others (P< 0.05), while STAT-3 was higher (P< 0.01).Conclusions HO-1 can be induced by CoPP and prolong the survival time of NIH-Wistar cardiac transplantation, which was probably related with STAT-3 activation and caspase-3 inhibition that results in the reduction of cardiac apoptosis.