他克莫司对脂肪肝供体大鼠肝移植围手术期移植物功能保护作用的研














	
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他克莫司对脂肪肝供体大鼠肝移植围手术期移植物功能保护作用的研

Protective of fatty liver grafts with tacrolimus after rat orthotopic liver transplantation

王东,朱继业, 栗光明,冷希圣

Wang Dong,Zhu Jiye,Li Guangming

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【摘要】 目的 探讨他克莫司对脂肪肝供体大鼠肝移植围手术期移植物功能的保护作用及机制。 方法 建立脂肪肝供体Wistar大鼠肝移植模型,实验组与对照组受体大鼠分别在术中、术后注射他克莫司(0.3 mg/kg)或生理盐水,在移植物再灌注0 h24 h72 h1周后分别检测两组受体大鼠的血清肝酶 [丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、乳酸脱氧酶(LDH)]、内皮素(ET)和脂质过氧化指标[超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和丙二醛(MDA],同时取肝组织制成匀浆检测其SODCATMDA水平,取小块肝组织制成切片在电镜下观察肝脏超微结构,采用原位末端标志法(TUNEL)检测肝组织的细胞凋亡情况。 结果 实验组大鼠的血清ALTASTLDHETMDA水平明显低于对照组,SODCAT高于对照组(P<0.05),实验组大鼠的肝组织匀浆中MDA水平也显著低于对照组,SODCAT高于对照组(P<0.05)。实验组肝脏超微结构的损伤程度和细胞凋亡程度均较对照组有所减轻。结论 他克莫司能在一定程度上保护脂肪肝供体大鼠肝移植围手术期移植物的功能,其作用机制可能与其抑制脂质过氧化、细胞凋亡和减轻再灌注损伤有关。

The investigation of the pProtective role of tacrolimus on the graft function following operation in rat orthotopic liver transplantion model with fatty liver donor. WANG Dong,ZHU Ji-ye,LI Guang-ming,et al. Department of hepatobiliary surgery,Peking University,People’s hospital, Beijing 100044,China.

[Abstract]  Objective To investigate the protective role and possible mechanism of tacrolimus on the graft function following operation in rat orthotopic liver transplantation model with fatty liver donor. Methods Orthotopic liver transplantation with fatty liver donor in Wistar rats were established,rats in experimental group were injected with tacrolimus (0.3 mg/kg) while control group with normal saline during and post transplantation. The serum levels of hepatic enzymes (ALT、AST、LDH)、ET、and lipid peroxidation index (SOD、CAT、MDA) were detected at 0 hour、24 hour、72 hour and 1 week time point following liver transplantation, and lipid peroxidation index was also detected in liver tissue homogenate at the same time point in these two groups. Ultramicroscopic morphological changes of liver tissue were checked under electron microscope,and cellular apoptosis of liver were checked by TUNEL method. Results The serum levels of ALT、AST、LDH、ET and MDA in experimental group were significantly lower than those in control group (P<0.05),while SOD and CAT levels were higher than control (P<0.05). The tissue homogenate level of SOD in experimental group was also reduced when compared with the control group (P<0.05), while SOD and CAT levels were higher than control (P<0.05) . The ultramicroscopic morphological damage of liver tissue and cellular apoptosis index in experimental group were better than control group as well. Conclusions Tacrolimus may have protective role of graft function in rat orthotopic liver transplantation with fatty liver donor to a certain extend. The possible mechanism is that tacrolimus may control the degree of lipid peroxidation, lessen cellular apoptosis and alleviate reperfusion injury.

关键词: 他克莫司;肝移植;边缘供体

中图分类号: R617

基金资助:

作者单位: 北京大学人民医院肝胆外科 北京大学器官移植中心

作者简介:

收稿日期: 2010-01-15

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