课题背景：作者在承担全军科研课题（01Q032）的研究工作中，从高过载反复暴露大鼠心脏组织中分离得到1组差异表达基因，其中在正加速度负荷反复暴露的大鼠心脏组织中血红素加氧酶1表达明显增加。

应用要点：实验观察了血红素加氧酶1对模拟移植后犬肺功能的影响。血红素加氧酶1过表达可增强肺组织抵抗氧化应激损伤，延长供体肺生存时间，改善移植后肺功能。这一结果为提高临床器官移植存活率提供了实验依据，为临床应用奠定了基础。

同行评价：血红素加氧酶1是一种应激性蛋白，通常应激性表达蛋白对机体都有保护性作用。肺移植保护也是临床迫切需要解决的重要问题。课题设计较合理，有一定创新性，对于研究移植肺保护具有重要意义。

摘要

背景：血红素加氧酶1是机体调节和抵抗氧化应激反应的重要生物分子，参与器官移植、缺血再灌注损伤等过程。
目的：应用犬离体肺移植再灌注模型模拟肺移植后的循环过程，观察预先诱导犬肺血红素加氧酶1过表达对模拟移植犬肺功能的影响。
设计、时间及地点：随机对照动物实验，于2005-12/2006-03在解放军空军总医院实验动物中心完成。
材料：健康杂种犬12只用于制备犬离体肺移植再灌注模型。
方法：按随机数字表法分3组（n=4）：模型组即单纯肺缺血再灌注组；诱导剂组和抑制剂组预先给予血红素加氧酶1诱导剂氯化血红素，抑制剂组于再灌注时向灌注液中加入血红素加氧酶1抑制剂锌原卟啉。
主要观察指标：比较分析各组犬肺组织中血红素加氧酶1 mRNA的表达水平，以及模拟移植后血气指标、肺动脉压、肺组织丙二醛含量和超氧化物歧化酶活性。
结果：12只犬全部进入结果分析。①诱导剂组血红素加氧酶1 mRNA 表达水平高于模型组和抑制剂组（P < 0.01）。②模拟移植后各组肺动脉压均呈先增高后降低的趋势，模拟移植后30 min左右肺动脉压达高峰。③模拟移植后120 min，诱导剂组动脉血氧分压高于模型组和抑制剂组（P < 0.05），动脉血二氧化碳分压低于模型组和抑制剂组（P < 0.05）；模型组与抑制剂组以上指标差异均无显著性意义（P > 0.05）。④模拟移植后120 min，各组丙二醛含量均升高，诱导剂组低于模型组和抑制剂组（P < 0.05）；各组超氧化物歧化酶活性均下降，诱导剂组高于模型组和抑制剂组（P < 0.05）。
结论: 过表达血红素加氧酶1能明显改善模拟移植的犬肺功能。
关键词：肺移植；血红素氧化酶；疾病模型，动物；器官移植

石缨，毕建立，宋志鸿，刘亚宁.血红素加氧酶1对模拟移植后犬肺功能的影响[J].中国组织工程研究与临床康复，2008，12(18):3432-3436 [www.zglckf.com/zglckf/ejournal/upfiles/08-18/18k-3432(ps).pdf]

Effect of heme oxygenase-1 effects on pulmonary function after simulant transplantation in dogs

Abstract

BACKGROUND: Heme oxygenase-1 (HO-1), an important biological molecular of regulating and resisting oxidative stress, participates in organ transplantation and ischemia/reperfusion injury.
OBJECTIVE: To observe the over-expression of heme oxygenase-1 (HO-1) on dog lung function after simulating cycle process in reperfusion models in dog ex vivo lung transplantation.
DESIGN, TIME AND SETTING: Randomized control animal experiments were performed at the Experimental Animal Center of Air Force General Hospital of Chinese PLA from December 2005 to March 2006.
MATERIALS: Twelve healthy hybrid dogs were used to establish reperfusion models in dog ex vivo lung transplantation.
METHODS: Dogs were randomly divided into three groups. Dogs in the model group received simple lung ischemia/reperfusion. Dogs in the inducer group were treated with heamin of HO-1 in advance. Dogs in the suppressant group underwent Zinc protoporphyrin (ZnPP) of HO-1 during reperfusion.
MAIN OUTCOME MEASURES: HO-1 mRNA levels, and after transplantation blood gas index, pulmonary artery press, superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents were detected in dog lung tissues in the three groups.
RESULTS: Totally 12 dogs were included in the final results. HO-1 mRNA levels of lung tissues increased in the inducer group compared to the suppressant group and model group (P < 0 .01). Pulmonary arterial pressure increased and then reduced in each group after transplantation, and reached a peak at about 30 minutes after simulant transplantation. 120 minutes after simulant transplantation, partial pressure of oxygen in artery (PaO2) was higher in the inducer group than in the model group and suppressant group (P < 0.05), but partial pressure of carbon dioxide in artery (PaCO2) was lower than in the model group and suppressant group (P < 0.05). No significant difference in above-mentioned indexes was detected in the model group and suppressant group (P > 0.05). 120 minutes after simulant transplantation, MDA contents were increased in each group, and were lower in the inducer group than in the model group and suppressant group (P < 0.05). SOD activities were reduced in each group, and were higher in the inducer group than in the model group suppressant group (P < 0.05).
CONCLUSION: The over-expressions of HO-1 can significantly improve the dog lung function after simulant transplantation.

Shi Y, Bi JL, Song ZH, Liu YM. Effect of heme oxygenase-1 effects on pulmonary function after simulant transplantation in dogs.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(18):3432-3436(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-18/18k-3432(ps).pdf]