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血管紧张素转换酶2在大鼠移植肝保存性损伤中的表达及意义
夏春燕1,刘惠敏1,李玲2,施晓敏3,徐毅1,丛文铭4*
0
(1.第二军医大学长征医院病理科,上海 200003;2.第二军医大学药学院药理学教研室,上海 200433;3.第二军医大学长征医院器官移植中心,上海 200003;4.第二军医大学东方肝胆外科医院病理科,上海 200438)
摘要:
目的:观察血管紧张素转换酶2(ACE-2)在大鼠移植肝中的表达及其与移植后保存性损伤(PI)的相关性,初步探讨局部肾素-血管紧张素系统(RAS)在肝移植PI中的可能作用。方法:根据供体肝冷保存时间将移植大鼠分为冷保存(CP)组及未进行冷保存(NCP)组,未进行肝移植的假手术组作对照;组织学检查观察肝脏保存性损伤程度,实时定量RT-PCR、蛋白质印迹、免疫组化法分别检测术后1、24、48 h肝组织ACE-2的mRNA、蛋白水平表达及其组织定位,哌莫硝唑免疫组化染色检测组织缺氧程度。结果:肝移植后存在不同程度组织损伤,CP组更明显;与假手术组相比,肝移植组术后ACE-2 mRNA及蛋白水平均显著升高(P<0.01或P<0.05),且CP组明显高于NCP组(P<0.05);免疫组化染色显示移植组在肝静脉周围呈阳性表达,染色阳性程度与ACE-2 mRNA表达明显正相关(r=0.78,P<0.001)。结论: ACE-2表达与冷保存导致的移植肝保存性损伤的组织缺氧密切相关,局部RAS可能参与了移植肝保存性损伤。
关键词:  血管紧张素转换酶2;肝移植;器官保存  保存性损伤
DOI:10.3724/SP.J.1008.2009.0757
投稿时间:2009-03-05修订日期:2009-03-30
基金项目:上海市卫生局科研课题基金(2007081).
Expression of angiotensin-converting enzyme 2 is increased during preservation injury of liver transplantation in rats
XIA Chun-yan1,LIU Hui-min1,LI Ling2,SHI Xiao-min3,XU Yi1,CONG Wen-ming4*
(1.Department of Pathology,Changzheng Hospital,Second Military Medical University,Shanghai 200003,China;2.Department of Pharmacology,School of Pharmacy,Second Military Medical University,Shanghai 200433; 3.Center of Organ Transplantation,Changzheng Hospital,Second Military Medical University,Shanghai 200003;4.Department of Pathology,Eastern Hepatobiliary Hospital,Second Military Medical University,Shanghai 200438)
Abstract:
Objective:To observe the expression of local angiotensin-converting enzyme 2 (ACE-2) in rat liver and its relationship with preservation injury (PI) after transplantation,so as to determine the possible role of local renin-angiotensin system (RAS) in PI caused by the cold-preservation in liver transplantation.Methods:The donor liver grafts were divided into cold preservation (CP) and non-cold preservation (NCP) groups;we also included a sham operation group without transplantation.The mRNA and protein levels of ACE-2 in the transplanted livers were detected by quantitative real-time PCR and Western blotting assay,respectively.The location of ACE-2 protein and pimonidazole in liver was detected by immunohistochemistry.Furthermore,histological evaluation was applied to verify the extent of liver damage.Results:Histological injuries of different degrees existed after liver transplantation; the injury was more obvious in the CP group.Compared with the sham operation group,the mRNA and protein expression of ACE-2 was significantly increased after liver transplantation (P<0.05 or P<0.01),and the expression of the CP group was significantly higher than that of the NCP group (P<0.05).Pimonidazole staining was positive around the hepatic veins in the transplantation groups,and the intensity of staining was positively correlated with the expression of ACE-2 mRNA (r=0.78,P<0.001).Conclusion:It is indicated that ACE-2 expression is closely associated with tissue hypoxia during cold preservation-induced PI ,and local RAS may play an important role in PI during liver transplantation.
Key words:  angiotensin-converting enzyme 2  liver transplantation  organ preservation  preservation injuries