Song Ning, Ni Quan-xing, Zhang Qun-hua, Shi Chang-qing, Rui Xiao-hui, Shi Liu-bin, Shi Wei
Department of Surgery, Huashan Hospital & Institute of Organ Ttransplantation, Fudan University, Shanghai 200040, China.
Zhonghua Yi Xue Za Zhi. 2005 Jun 29;85(24):1674-8.
To investigate the effects and mechanism of heme oxygenase-1 (HO-1) in liver xenotransplantation and mechanism thereof.
Thirty male guinea-pigs used as donors were injected intravenously with cobra venom factor (CVF) and then randomly divided into 3 groups 24 hours after: Group A injected intraperineally with NaCl, Group B injected intraperineally with cobalt-protoporphyrin (CoPP), heme oxygenase-1 inducer, and Group C injected intraperineally with CoPP and zinc protoporphyrin (ZnPP), HO-1 inhibitor zinc before their livers were harvested. Thirty male SD rats used as recipients underwent the above-mentioned treatment 24 hours before receiving the xenografts. Five pairs of guinea pigs and rats in each group underwent collection of blood and liver tissues 3 hours after the recovery of blood perfusion in the transplanted livers for detection of serum enzymes by biochemical methods and expression of HO-1 mRNA and protein in the transplanted livers by RT-PCR and Western blotting respectively. The other 5 pairs in each group were used to observe the survival time.
The survival time of Group B was 15.5 h +/- 3.8 h, significantly longer than those of Group A (7.3 h +/- 2.1 h) and Group C (6.7 h +/- 2.9 h, both P < 0.01). The values of ALT and LDH of Group B were significantly lower than those of Group A and C (all P < 0.05). HOI-1 mRNA expression was not detected or only expressed in trace amount in the livers of normal guinea pigs, expressed in a small amount in the transplanted livers of Group A. The expression of HO-1 mRNA and that of HO-1 protein in the transplanted livers of Group B were significantly higher than those of Group A (both P < 0.01), and the expression of HO-1 mRNA and that of HO-1 protein in the transplanted livers of Group C were not significantly different from those of Group A (both P > 0.05). Remarkable NF-kB band was detected in Groups A and C, and only weak NF-kB band was seen in Group B. The E-selectin expression was significantly lower in the transplanted livers of Group B than in those of Group A and C (both P < 0.05).
HO-1 delays the occurrence of delayed xenograft rejection in liver xenotransplantation. This effect depends, at least in part, on HO-1-mediated inhibition of endothelium activation in xenografts.
探讨血红素加氧酶-1（HO-1）在肝异种移植中的作用及其机制。
30只雄性豚鼠作为供体，静脉注射眼镜蛇毒因子（CVF），24小时后随机分为3组：A组腹腔注射氯化钠；B组腹腔注射血红素加氧酶-1诱导剂钴原卟啉（CoPP）；C组腹腔注射CoPP及HO-1抑制剂锌原卟啉（ZnPP），然后摘取肝脏。30只雄性SD大鼠作为受体，在接受异种移植前24小时进行上述处理。每组5对豚鼠和大鼠，在移植肝脏恢复血流灌注3小时后采集血液和肝组织，分别用生化方法检测血清酶，用RT-PCR和Western印迹法检测移植肝脏中HO-1 mRNA和蛋白的表达。每组另外5对用于观察生存时间。
B组生存时间为15.5小时±3.8小时，显著长于A组（7.3小时±2.1小时）和C组（6.7小时±2.9小时，均P<0.01）。B组ALT和LDH值显著低于A组和C组（均P<0.05）。正常豚鼠肝脏未检测到HO-1 mRNA表达或仅微量表达，A组移植肝脏中HO-1 mRNA少量表达。B组移植肝脏中HO-1 mRNA和HO-1蛋白表达均显著高于A组（均P<0.01），C组移植肝脏中HO-1 mRNA和HO-1蛋白表达与A组无显著差异（均P>0.05）。A组和C组检测到明显的NF-κB条带，B组仅见微弱的NF-κB条带。B组移植肝脏中E-选择素表达显著低于A组和C组（均P<0.05）。
HO-1可延缓肝异种移植中延迟性异种移植排斥反应的发生。这一作用至少部分依赖于HO-1介导的对异种移植中内皮细胞活化的抑制。
