| | | 川芎嗪对大鼠移植肝的保护作用
| | 免费中药学论文 作者:刘胜雄，欧阳永忠，汤明，吴飞跃
【摘要】 目的免费中药学论文 探讨川芎嗪（TMP）对大鼠移植肝的免费中药学论文保护作用。方法 参照Delriviere和Kamada等方法建立大鼠肝移植模型，将大鼠随机分为3组：A组（假手术组）、B组（肝移植对照组）和C组（TMP干预组）。采用全自动生化分析仪检测术后血清肝功能(AST、ALT、LDH)水平；应用免疫组化SP法结合病理图像分析仪测定肝组织中Bcl-2、Bax的表达情况；HE染色观察其病理形态学变化。结果 （1）C组AST、ALT、LDH明显低于B组（P<0.01）。（2）C组Bcl-2或Bcl-2/Bax表达明显高于B组（P<0.05），而Bax表达无明显变化（P>0.05）。（3）A组无明显病理形态改变，B组术后肝组织出现明显的病理损害，C组病理变化明显减轻。结论 TMP可能通过上调Bcl-2或Bcl-2/Bax表达而减轻肝移植体的低温保存再灌注损伤，对供肝有保护作用。
【关键词】 肝移植；保存再灌注损伤；川芎嗪；Bcl-2；Bax
Protective effect of tetramethylpyrazine on liver graft in rat liver transplantation
【Abstract】 Objective To investigate the protective effect of tetramethylpyrazine (TMP) preconditioning on liver graft in rat liver transplantation.Methods Performing the operation of liver transplantation in male Sprague-Dawley rats referred to Delriviere and Kamada with cuff anastomosing methods，the rats were randomly divided into three groups：A group(n=6，sham operation group)，B group (n=30×2，liver transplantation control group)，C group (n=30×2，TMP group).The parameters of liver function (AST，ALT and LDH) were tested by auto-biochemical analyser in group B and C after reperfusion 0.5h，3h，6h，24h，48h respectively via the plasma samples；part of the liver tissue was sampled to determine the expression of Bcl-2 and Bax.The parameters in group A were examed 3h after the operation.The expression of Bcl-2 and Bax was determined by immunohistochemisty technique with pathological imaging analyser.Also，parts of liver tissue samples were used to detect the histopathologic changes.Results （1）The levels of AST，ALT and LDH were significantly decreased in group C compared with that in group B （P＜0.01）after reperfusion 0.5h，3h，6h，24h，48h respectively.（2）The expression of Bcl-2 were significantly increased in group C compared with that in group B （P＜0.01）after reperfusion 0.5h，3h，6h respectively.The different expression of Bax between group C and group B was nonsignificant.（3）Approximately normally morphologic structure was found in group A，some obvious histopathologic changes in group B could be seen morphologically.But in group C，some histopathologic changes were alleviated.Conclusion TMP can improve liver function and alleviate histopathologic damage in liver transplantation in rats during preservation and reperfusion injury probably by up-regulating the expression of Bcl-2 or Bcl-2/Bax and exert a protective effect on liver graft.
【Key words】 liver transplantation；preservation and reperfusion injury；tetramethylpyrazine；Bcl-2；Bax
肝移植是治疗终末期肝病最有效的手段，肝移植体低温保存再灌注损伤是肝移植术后肝原发性无功能（PFN）的重要原因，与细胞凋亡密切相关。目前人们针对凋亡发生的各个环节，探索各种防治方法，从而减轻肝移植体保存再灌注损伤成为了研究的热点。川芎嗪（tetramethylpyrazine，TMP，四甲基吡嗪）是从中药川芎中分离、纯化的一种生物碱，TMP具有抑制血小板的聚集、改善微循环、保护血管内皮细胞、对抗氧自由基的氧化作用以及钙拮抗作用；TMP作为钙拮抗剂，可能通过激活腺苷酸环化酶及抑制钙离子内流作用而抑制细胞凋亡［1］；TMP还可以影响c-fos表达而抑制细胞凋亡［2］。但目前TMP在细胞内的分子机制研究甚少，需进一步研究。TMP是否影响移植肝保存再灌注损伤细胞凋亡调控基因的表达，尚未见报道。本实验通过建立大鼠肝移植模型，观察TMP对保存再灌注损伤中肝组织Bcl-2、Bax表达的影响，探讨TMP对大鼠移植肝的保护作用。
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