南方医科大学学报2012,Vol.32Issue(9):1301-1306,6.DOI:10.3969/j.issn.1673-4254.2012.09.019
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
摘要
Abstract
Objective To investigate the effect of pretreatment with ulinastatin on livet 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 Dl, 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-a and IL-6 were significantly lower, and IL-6 level and the expressions of STAT-3, cyclin Dl, and Cdk4 mRNA and cyclin Dl 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 Dl-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Key words
liver/ ischemia reperfusion injury/ regeneration/ ulinastatin/ signal pathway分类
医药卫生引用本文复制引用
朱宇麟,周荣胜,杨会,谭敬,张晓琪,刘齐宁..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[J].南方医科大学学报,2012,32(9):1301-1306,6.基金项目
陕西省科技攻关项目(2008K14-02) (2008K14-02)
天普研究基金项目(012009040) (012009040)