诱导血红素加氧酶-1高表达对大鼠减体积肝移植生存的影响  

The effect of heme oxygenase-1 overexpression on the survival of rat reduced-size liver transplantation

作　　者：肖江卫[1] 金先庆[2] 王崇树[1] 王城[1] 李忆秋[1] 

机构地区：[1]川北医学院附属医院普外科,南充637000 [2]重庆医科大学附属儿童医院普外科

出　　处：《中华小儿外科杂志》2006年第10期545-550,共6页Chinese Journal of Pediatric Surgery

摘　　要：目的为了明确血红素加氧酶-1的高表达对大鼠减体积肝移植生存的影响,进而探索出一条有效地防止小体积移植肝缺血再灌注损伤的方法。方法利用分子生物学方法构建携带有HO-1基因的重组腺病毒Ad5-HO-1,对供体进行预处理,并观察Ad5-HO-1对大鼠小体积移植肝缺血再灌注损伤的保护作用。结果Ad5-HO-1组与对照组相比较ALT水平有显著降低(P＜0．05)；术后2 h内门静脉血流流量有明显增加(P＜0．05)；HO-1酶活性测定显示Ad5-HO-1组酶活性为(5．34±0．41)×10^(-3)mmol·mg^(-1)·mm^(-1),较对照组明显为高(P＜0．05)；RT-PCR和免疫组化检测HO-1、TNF-α、Bcl-2、Bax表达,证实Ad5-HO-1组中HO-1、Bcl-2的表达是增高的,而Bax、TNF-α表达是降低的(P＜0．05)；Ad5-HO-1组在1、7、21d的生存率分别为100%、85．7%、71．4%,而对照生理盐水组在1、7、21 d的生存率分别为66．7%、16．7%、16．7%(P＜0．05)。结论Ad5-HO-1的应用能够显著地增加术后2 h内门静脉血流,有利于受体术后肝功能的恢复,从而改善大鼠移植术后的生存结果。实验结果提示HO-1的高表达在防止和减轻小肝移植物缺血再灌注损伤的过程中扮演着重要的角色,进而为临床上防止小肝移植物缺血再灌注损伤提供了一条新的思路和方法。Objective To clarify the role of heme oxygenase-1（HO-1） over-expression in the survival of rat reduced-size liver transplantation Methods We generated recombinant adenoviral vector encoding HO-1 gene （AdS-HO-1） by the standard molecular biological method. And the AdS-HO- 1 was administered to donors via vein at 48 hours before transplantation Livers of donors were harvested and stored for 24 h at 4 ℃ in HTK solution before they were implanted into recipients. The survival rate and survival time of the recipients were recorded. The expressions of HO-1, TNF-α, Bcl- 2 and Bax in the livers were shown by RT-PCR and immunohistochemical staining. Results Compared with controls, The level of serum ALT in the AdS-HO-1 group was significantly reduced（P〈0. 05）, while portal venous blood flow（PVBF） was significantly increased within 2 hours after transplantation （P〈0. 05）. The activity of HO-1 in the Ad5-HO-1 group was significantly higher than that in control group （P〈0. 05）. The expressions of HO-1 and Bcl-2 in AdS-HO-1 treatment group were much higher than those in the controls, while the expressions of TNF-α and Bax were lower than those in controis. At the 1^st, 7^th, and 21^th day after operation, the survival rate in the Ad5-HO-1 was 100%, 85. 7%, and 71.4% while in the control group was 66. 7%, 16. 7%, and 16. 7%, respectively（P〈 0. 05）. Conclusions HO-1 may play an important protective role in the rat reduced-size liver transplantation.

关 键 词：血红素加氧酶-1 肝移植 缺血再灌注损伤 

分 类 号：R726.5[医药卫生—儿科]