血红素加氧酶-1高表达对大鼠同种异体肺移植物缺血再灌注损伤的保护作用  

Endogenous Heme Oxygenase-1 Overexpression Protects Rat Lung Allografts from Ischemia Reperfusion Injury

作　　者：林江波[1] 康明强[1] 陈道中[2] 陈椿[1] 林若柏[1] 

机构地区：[1]福建医科大学附属协和医院胸外科,福州350001 [2]福建医科大学附属协和医院心外科,福州350001

出　　处：《福建医科大学学报》2012年第1期15-19,共5页Journal of Fujian Medical University

摘　　要：目的观察原卟啉钴(CoPP)诱导内源性血红素加氧酶-1(HO-1)高表达对大鼠同种异体左肺移植物缺血再灌注损伤(IRI)的影响及其作用机制。方法以SD大鼠为供受体,采用改良三袖套法技术建立同种异体左肺移植模型。设立空白对照组(A组)、CoPP+原卟啉锌(ZnPP)组(B组)和CoPP组(C组),离体供肺静脉4℃的LPDG液逆行灌注,供肺保存3h后移入受鼠,移植肺再灌注4h后阻断右肺门,测量动脉血PaO2及PaCO2。取移植肺测肺湿/干质量比率(W/D)、超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及髓过氧化物酶(MPO)活性;观察病理组织学变化;PCR和免疫组织化学测HO-1表达;酶联免疫吸附法(ELISA)测TNF-a量的变化;TUNEL法检测移植肺细胞凋亡水平。结果与A、B组比较,C组HO-1升高,PaO2上升、肺W/D下降,SOD活性增高,MDA、TNF-a含量和MPO活性下降(P<0.01);肺泡间质水肿明显减轻,炎症细胞浸润减少,肺泡腔内水肿液和红细胞少见,细胞凋亡减少(P<0.01)。结论 CoPP诱导移植肺高表达内源性HO-1,后者通过抗氧化、抗炎和抗凋亡等多种途径减轻供肺IRI,提高肺移植术后早期肺功能。Objective To investigate the effect of endogenous heme oxygenase-1 overexpression by using CoPP as the HO-1 inducer on ischemia reperfusion injury of rat left lung allograft and explore the mechanisms.Methods A left lung transplantation formwork was constructed by using SD rat both donor and recipient by improved muff-like technique.Three groups of rats were examined.At 24 hours before the harvest,the donors in group A,which is the control group,received 0.9% saline,the donors in group B were pretreated with CoPP＋ZnPP,the donors in group C received CoPP.The donor lungs were all ex vivo reperfused by 4 ℃ LPDG through pulmonary vein.After the left lung allograft was reperfused for 4 hours,we blocked the hilum of right lung,and made arterial blood gas analysis to measure PaO2 and PaCO2.At last,rat was executed.Lung allograft tissue was harvested to be detected.W/D ratio,superoxide dismutase（SOD） activity,malondialdehyde（MDA） contents and myeloperoxidase（MPO） activity were detected.Graft pathologic histology was examined under light microscope.The message of expression of HO-1 in donor lung tissue was measured by immunohistochemical staining and reverse transcription-polymerase chain raction（RT-PCR）.The content of TNF-a was quantified by ELISA.Apoptotic cell death was determined by TUNEL.Results The contents of HO-1 in group C was obviously higher than that in groups A and B（P0.01）.Compared with groups A and B,PaO2 and the activity of SOD increased.W/D ratios,content of MDA,the level of TNF-a and activity of MPO decreased（P0.01）.In group C,tissue edema,interstitial inflammation and exudation alleviated under light microscope.Less apoptotic cells were found by TUNEL（P0.01）.Conclusion The efficient expression of endogenous heme oxygenase-1 overexpression by using CoPP was demonstrated.HO-1 has the characters of anti-oxidative,anti-inflammatory and anti-apoptosis,which down-regulate the expression of TNF-a,and can reduce interstitial inflammation,graft inflammatory reaction and cellular a

关 键 词：肺移植 肺 再灌注损伤 血红素加氧酶-1 大鼠 Sprague-Dawley 

分 类 号：R-332[医药卫生] R332.2