他克莫司对移植肝脏再灌注损伤的影响  

Effects of tacrolimus on reperfusion injury in orthotopic liver transplantation

作　　者：王东[1] 朱继业[1] 栗光明[1] 黄磊[1] 朱凤雪[1] 冷希圣[1] 

机构地区：[1]北京大学人民医院肝胆外科、北京大学器官移植中心,100044

出　　处：《中华消化外科杂志》2008年第2期112-115,共4页Chinese Journal of Digestive Surgery

摘　　要：目的探讨他克莫司对移植肝脏再灌注损伤的影响。方法建立大鼠肝移植模型，实验组（40只）和对照组（40只）分别注射他克莫司和生理盐水，检测再灌注24、48和96h后TNF-α、IL-1、ALT、AST、LDH、内皮素（endothelin，ST）和丙二醛（malondialdehyde，MDA）水平，观察肝脏超微结构和细胞凋亡情况，RT-PGB法检测Fas、Bcl-2的mRNA水平。依据免疫抑制方案，将112例终末期肝硬化患者分为他克莫司组（63例）和环孢素A组（49例），比较临床肝移植使用环孢素A和他克莫司患者肝酶指标及急性排斥反应的发生。结果实验组TNF-d、IL-1、ALT、AST、LDH、ET和MDA显著低于对照组（P〈0．05），肝脏超微结构受损和细胞凋亡较轻，Fas mRNA合成减少。患者使用他克莫司后急性排斥反应发生率较环孢素A低（x^2=39．0，P〈0．05）。结论他克莫司可通过抑制细胞凋亡来减轻大鼠移植肝脏再灌注损伤，临床使用他克莫司能减少急性排斥反应的发生。Objective To investigate the effects of tacrolimus on reperfusion injury in orthotopic liver transplantation. Methods The rat models of orthotopic liver transplantation were established. SD rats in experimental group （ n = 40） were injected with tacrolimus while control group （ n = 40） with normal saline. The serum levels of TNF-α, IL-1, ALT, AST, LDH, endothelin （ET） and malondialdehyde （MDA） were detected at 24, 48, 96 hours after reperfusion. Ultrastructural changes and cellular apoptosis of liver and synthesis of mRNA of Fas and Bcl-2 were checked. According to the immunosuppression regimen, 112 patients with end-stage liver cirrhosis were divided into taerolimus group （ n = 63） and cyclosporin A group （ n = 49）. The levels of hepatic enzymes and the rate of acute rejection in patients of the two groups after liver transplantation were compared. Results Levels of TNF-α, IL-1, ALT, AST, LDH, ET and MDA in experimental group were significantly lower than those in control group （ P 〈 0.05 ）. Rats in experimental group had less Fas mRNA synthesis, minor liver ultrastructure lesion and cellular apoptosis than control group. Compared with cyclosporin A group, acute rejection was decreased in taerolimus group （ X^2 = 39.0, P 〈 0.05）. Conclusions Tacrolimus may lessen reperfusion injury and cellular apeptosis in rat orthotopic liver transplantation, and it may also alleviate reperfusion injury in human liver transplantation and reduce the rate of acute rejection.

关 键 词：肝移植 再灌注损伤 他克莫司 

分 类 号：R285.5[医药卫生—中药学]