乌司他丁对肝大部切除合并缺血再灌注损伤后肝再生及TNF-α/IL-6/STAT-3信号通路的影响  

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

作　　者：朱宇麟[1] 周荣胜[1] 杨会[1] 谭敬[1] 张晓琪[1] 刘齐宁[1] 

机构地区：[1]西安交通大学医学院第一附属医院麻醉科,陕西西安710061

出　　处：《南方医科大学学报》2012年第9期1301-1306,共6页Journal of Southern Medical University

基　　金：陕西省科技攻关项目(2008K14-02);天普研究基金项目(012009040)

摘　　要：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230～280g，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／坌日。PH组不阻断残肝血流；PHIR组阻断血流30min后恢复灌注；UTI组于缺血前5min经尾静脉给予UTI50000U／kg。再灌注后1、6、12、24、48h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〈O．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24h和48hSTAT-3、CyclinD1、Cdk4mRNA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。Objective To investigate the effect of pretreatment with ulinastatin on liver regeneration and TNF-α/IL-6/STAT-3 signal pathway in rats after 70% hepatectomy combined with ischemia-reperfusion injury. Methods A total of 120 normal male SD rats weighing 230-280 g were randomized into 3 groups （n=40）, namely simple partial hepatectomy （PH） group, partial hepatectomy with ischemia-reperfusion （PHIR） group, and ulinastatin group. All the rats received resection of the left and middle liver lobes. In PHIR group, the remnant right lobes were subjected to blood flow occlusion for 30 min; in UTI group, the rats were given 50 000 U/kg UTI intravenously prior to the occlusion, and in PH group, the blood flow was not occluded. At 1, 6, 12, 24, and 48 after the reperfusion, the remnant liver tissues were examined for regenerated liver weight, PCNA staining, TNF-α and IL-6, STAT-3, cyclin D1, and Cdk4 expressions. Results The regenerated liver weight and PCNA positivity rates were significantly higher in ulinastatin group than in PHIR group at 24 h and 48 h after the reperfusion （P〈0.05）. In ulinastatin group, the levels of TNF-α and IL-6 were significantly lower, and IL-6 level and the expressions of STAT-3, cyclin D1, and Cdk4 mRNA and cyclin D1 and Cdk4 proteins were significantly higher in ulinastatin group than in PHIR group at 24 h and 48 h （P〈0.05）. Conclusion Unilatatin can promote liver regeneration after major hepatectomy and ischemia-reperfusion injury, and the effect is possibly related with activation of IL-6/STAT-3 signal pathway, which promotes the synthesis of cyclin D1-Cdk4 complex and hepatocyte proliferation.

关 键 词：肝脏 缺血再灌注损伤 再生 乌司他丁 信号通路 

分 类 号：R657.3[医药卫生—外科学]