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干扰素调节因子1对小鼠肝脏缺血再灌注损伤的影响 被引量:1

IRF-1' role in liver ischemia reperfusion injury in mice
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摘要 目的研究干扰素调节因子1(IRF-1)对小鼠肝脏缺血再灌注(IR)损伤的影响及机制,寻求减轻肝脏缺血再灌注损伤的有效方法。方法将小鼠分为对照组(假手术组)、小鼠肝脏热IR损伤模型组(IR组)和重组IRF-1干预组(IRF-1组),构建小鼠肝脏缺再灌注损伤模型。检测假手术组和IR组小鼠IRF-1的mRNA和蛋白水平、肝功能和肝组织病理变化;检测IR组和IRF-1组IR损伤6h后肝细胞IRF-1、p-Statl、p-P38、PARP1与Caspase-3蛋白水平的变化以及增殖细胞核抗原(PCNA)表达情况。结果小鼠肝脏缺血再灌注后,肝组织IRF-1 mRNA和蛋白表达水平均显著升高,再灌注6h时达到峰值,与假手术组相比,差异有统计学意义(t再灌注2h=-3.512、t再灌注6h=-4.247、t再灌注12h=-4.088、t再灌注24h=-3.851;P〈0.05);IR组小鼠血清ALT、AST水平(tALT=4.931、4.592、4.277、4.809;tAST=4.980、4.617、4.336、4.915;P〈0.05)在各个时间点均高于假手术组,肝脏病理学改变亦比假手术组明显加重。使用重组IRF-1干预后,肝细胞中IRF-1、p-Stat1、p-P38、PARP1与Caspase-3蛋白水平均升高,PCNA表达减少。结论IRF—1表达与肝脏缺血再灌注损伤密切相关,其机制可能与廊激活化蛋白激酶(JNKMAPK)的激活及抑制PCNA表达有关。 Objective To investigate the role of interferon regulatory factor-1 (IRF-1) in liver ischemia/reperfusion (IR) injury and its underlying mechanism, and identify effective managements in alleviating liver IR injury. Methods Three groups of mice models with liver IR injury were well established, including control group (S), warm liver IR injury group (IR) and recombinant IRF-1 group (IRF-1). The levels of mRNA and protein, liver function and pathological changes of liver tissue were detected in group S and group IR. Additionally, the marker of IRF-1, p-Statl, p-P38, PARP1 and Caspase-3 were measured and PCNA expression was determined in group IR and group IRF-1 mice with 6-hour liver IR injury. Results IRF-1 mRNA and protein and the levels expression of proteins were significantly elevated with peak occurred after 6-hour IR injury, which was statistic difference compare to the group S ( t2h = - 3. 512, t6h = -4. 247, t12h = -4. 088, t24h = -3. 851 ; P 〈0.05). Serum ALT and AST of mice detected in group IR were higher than group S at all endpoints (tALT =4.931, 4.592, 4.277, 4.809; tAST =4.980, 4.617, 4.336, 4.915; P 〈 0.05 ). Furthermore, pathological damage change was more distinct compared with group S. The elevated levels of IRF-1, p-Stat1, p-P38, PARP1 and Caspase-3 and decreased PCNA expression were determined in mice models with recombinant IRF-1 intervention. Conclusion IRF-1 expression could be closely correlated with liver IR injury, and its underlying mechanism may be attributed to activation of JNK MAPK pro- tein and inhibition of PCNA expression.
出处 《中华肝胆外科杂志》 CSCD 北大核心 2017年第4期255-258,共4页 Chinese Journal of Hepatobiliary Surgery
基金 国家自然科学基金面上项目(81370576) 天津市卫生局科技基金重点项目(2013KR05)
关键词 肝脏缺血 缺血再灌注 再灌注损伤 干扰素调节因子-1 Liver ischemia Ischemia-reperfusion Reperfusion injury Interferon regulatory factor-1 ( IRF-1 )
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