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Effect of ulinastatin pretreatment on liver regeneration and TNF-α/IL-6/STAT-3 signal pathway in rats with major hepatectomy and ischemia-reperfusion injury

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Author:
No author available
Journal Title:
Journal of Southern Medical University
Issue:
9
DOI:
10.3969/j.issn.1673-4254.2012.09.019
Key Word:
肝脏;缺血再灌注损伤;再生;乌司他丁;信号通路

Abstract: 目的 探讨乌司他丁(UTI)预处理对大鼠70%肝切除合并缺血再灌注损伤后残肝再生和TNF-α/IL-6/STAT-3信号通路的影响.方法 健康清洁级雄性SD大鼠120只,体质量230~280 g,随机分为单纯肝切除组(PH)、肝切除合并缺血再灌注组(PHIR)和乌司他丁组(UTI),40只/组.PH组不阻断残肝血流;PHIR组阻断血流30 min后恢复灌注;UTI组于缺血前5min经尾静脉给予UTI 50 000 U/kg.再灌注后1、6、12、24、48 h取各组大鼠残肝组织,测定残肝再生度、PCNA阳性率,TNF-α、IL-6水平,STAT-3、CyclinD1、Cdk4mRNA表达及CyclinD1、Cdk4蛋白表达水平.结果 UTI组24h和48h肝再生度和PCNA阳性率较PHIR组显著升高(P<0.05);UTI组早期TNF-α、IL-6水平较PHIR组显著降低(P<0.05),但再灌注晚期IL-6水显著高于PHIR组(P<0.05);UTI组24 h和48 h STAT-3、CyclinD1、Cdk4 mRNA表达及CyclinD1和Cdk4蛋白表达水平均显著高于PHIR组(P<0.05).结论 乌司他丁对肝大部切除合并缺血再灌注损伤后残肝的再生具有促进作用,其机制与激活IL-6/STAT-3信号通路,促使肝细胞CyclinD1-Cdk4复合物合成,促进肝细胞增殖有关.

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