β-catenin基因在小鼠肝脏缺血再灌注损伤中的保护作用及机制  

Protective role of β- catenin gene in hepatic ischemia- reperfusion injury among mice and its mechanism

作　　者：孙克彦[1] 滕飞[1] 郭闻渊[1] 刘芳[1] 傅志仁[1] 

机构地区：[1]第二军医大学附属医院长征医院移植科,上海200003

出　　处：《临床肝胆病杂志》2013年第10期787-789,共3页Journal of Clinical Hepatology

摘　　要：目的研究β-catenin基因对小鼠肝脏缺血再灌注损伤的保护作用及机制。方法建立特异性敲除β-catenin基因小鼠及部分肝脏缺血再灌注损伤模型,检测部分肝脏缺血再灌注后血清学指标ALT、AST及肝脏病理学改变,应用实时荧光定量聚合酶链反应(RT-PCR)技术测定β-catenin-/-组和野生型组小鼠再灌注6 h后肝组织内缺氧诱导因子(HIF)1α、肿瘤坏死因子(TNF)α、白细胞介素(IL)1β的mRNA表达水平。分析数据组间比较采用t检验或方差分析。结果β-catenin-/-组小鼠再灌注后病理损伤较野生型(WT)对照组严重,血清中ALT、AST水平明显高于WT组,(8178.61±78.76)vs(891.83±23.73)U/L,t=24.296;(7348.94±141.99)vs(873.50±20.27),t=27.854,P均<0.001。β-catenin-/-组肝组织HIF-1α的mRNA表达水平显著低于WT组,(0.31±0.04)vs(1.00±0.22),t=3.949,P<0.01。而TNFα、IL-1β的mRNA表达水平显著高于WT组(3.14±0.37)vs(1.00±0.19),t=3.676;(3.72±0.33)vs(1.00±0.24),t=4.017,P均<0.01。结论β-catenin基因缺失可通过影响HIF-1α表达加重肝脏缺血再灌注损伤。Objective To investigate the protective effect of β - catenin gene in hepatic ischemia - reperfusion injury among mice and the underlying mechanism. Methods Using β -catenin knockout mice and a segmental hepatic ischemia -reperfusion model, serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） and the pathological changes in the liver were evaluated after seg-mental hepatic ischemia - reperfusion, and the mRNA expression levels of hypoxia - inducible factor 1 α （ HIF - 1 α） , tumor necrosis factor - α （ TNFα）, and interleukin - 1 β （ IL - 1 β） in the liver tissues of β - catenin^ - / - mice and wild - type （WT） mice were determined by real - time fluorescence quantitative polymerase chain reaction six hours after reperfusion. Comparisons between groups were performed with the t test or analysis of variance. Results β - catenin^ -/- mice sustained severer pathological injury from ischemia - reperfusion than WT mice, as evidenced by significantly higher serum levels of ALT （8178.61 ± 78.76 U/L vs 891.83 ± 23.73 U/L, t = 24. 296, P 〈 0. 001 ） and AST （7348.94 ± 141.99 U/L vs 873.50 vs 20.27 U/L, t = 27. 854, P 〈 0. 001 ） and significantly higher mRNA expression levels of TNF-α （3.14±0.37 vs 1.00±0.19, t=3.676, P〈0.01） andIL-1β （3.72±0.33 vs 1.00±0.24, t=4.017, P〈0.01） in β- catenin^ -/- mice compared with WT mice. In contrast, the mRNA expression of HIF - 1α was down - regulated in β - catenin^ -/- mice rel- ative to WT mice （0.31 ± 0.04 vs 1.00 ± 0.22, t = 3. 949, P 〈 0.01 ）. Conclusion β - catenin gene deletion aggravates hepatic ischcmia - reperfusion injury by reducing the expression of HIF - 1α.

关 键 词：再灌注损伤 Β连环素 小鼠 

分 类 号：R657.3[医药卫生—外科学]