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他克莫司对移植肝脏再灌注损伤的影响 |
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【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96 h后TNF-α、IL-1、ALT、AST、LDH、内皮素（endothelin,ET）和丙二醛（malondialdehyde,MDA）水平，观察肝脏超微结构和细胞凋亡情况，RT-PCR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-α、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（χ2=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。
【关键词】 肝移植； 再灌注损伤； 他克莫司
Effects of tacrolimus on reperfusion injury in orthotopic liver transplantation WANG Dong, ZHU Ji-ye, LI Guang-ming, HUANG Lei, ZHU Feng-xue, LENG Xi-sheng.Department of Hepatobiliary Surgery, People′s Hospital, Peking University, Beijing 100044, China
【Abstract】 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 tacrolimus 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, acu[1] [2] [3] [4] 下一页
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