不同肝缺血时限肝硬化及非肝硬化肝组织基因差异表达及其意义  

Significances of gene differential expression patterns in hepatocirrhosis and non-hepatocirrhosis tissues within different ischemic time

作　　者：卢绮萍[1] 裘法祖[2] 吴在德[2] 曹庭加[1] 张智勇[1] 曹钧[1] 刘伟[1] 冯毓灵[1] 

机构地区：[1]广州军区武汉总医院普通外科,430070 [2]华中科技大学同济医学院同济医院

出　　处：《中华外科杂志》2007年第1期50-53,共4页Chinese Journal of Surgery

基　　金：国家自然科学基金(30170928);全军医学科研十五计划项目(01MA040)

摘　　要：目的探讨肝硬化和非肝硬化肝组织肝缺血不同时限基因差异表达,为合理掌握肝缺血安全时限提供理论依据。方法以正常肝组织为对照,将观测标本分为 A(非肝硬化)、B(肝硬化)两组,每组按不同缺血时限(分别为15、30、45 min)分3个亚组。标本取材后立即置入液氮冻存备测,应用4000点基因芯片分析不同缺血时限各组基因差异表达。结果肝缺血15 min,非肝硬化组基因表达谱变化以调控内环境稳定的编码基因表达上调为主,而肝硬化组则出现了多个凋亡相关基因的高表达。肝缺血30 min,两组肝组织凋亡相关基因表达均处高峰阶段,不同点在于:肝硬化组促凋亡基因表达的数量和 Ratio 值均大于非肝硬化组;非肝硬化组同期有多个热休克蛋白家族成员编码基因和抗氧化蛋白编码基因高表达。肝缺血45 min,肝硬化组与热休克蛋白和抗氧化蛋白编码基因均处于低表达水平。结论肝脏遭受缺血性损伤后决定细胞生存状态的关键时限点大约在30 min 左右;非肝硬化组织抗损伤能力较强,有可能耐受超过30 min 甚至更长的肝缺血时限;肝硬化组织肝缺血安全时限以控制在30 min 以内为宜。Objective To investigate the gene differential expression patterns in hepatocirrhosis and non-hepatocirrhosis tissues within different ischemic time. Methods The liver tissues were divided into two groups： Group A （ non-hepatocirrhosis）, Group B （ hepatocirrhosis ）, each of which consisted of 3 groups with different ischemic time： 15, 30 and 45 minutes. The gene differential expression patterns in the two groups within different ischemic time were detected and compared with those in normal liver tissues by using 4000 points gene microarray. Results In non-hepatocirrhosis tissues, the homeostatic maintenance genes expressed highly during hepatic ischemia for 15 minutes, and no apoptotic gene was expressed; but in hepatocirrhosis tissues, many apoptotic genes expressed highly. As for 30 minutes, in both two groups liver tissue genes expressed to the peak, and the genes related to cell death, oxidative stress and nuclear factors expressed highly. The difference lies in the facts that in Group B pro-apoptosis genes expressed more than those in Group A, and the Ratio values were higher than those in Group A. Many genes of heat shock protein family and antioxidant proteins expressed highly simultaneously in Group A, but comparatively low in Group B. As for 45 minutes, genes of heat shock proteins and antioxidant proteins expressed lowly in Group B. Conclusion It suggests that the safe time limit of hepatic ischemia for cell survive is 30 minutes or so. Non-hepatocirrhosis tissues could endure 30 minutes of ischemia and even longer, but it should be restricted within 30 minutes in hepatocirrhosis tissues.

关 键 词：肝硬化 局部缺血 基因表达 

分 类 号：R575.2[医药卫生—消化系统]