摘要
目的探讨缺血后处理对肝大部切除后合并缺血再灌注损伤余肝再生肿瘤坏死因子（TNF）α／IL-6／信号转导及转录激活因子（STAT）3信号通路的影响。方法健康清洁级雄性SD大鼠90只，体质量230～280g。随机分为三组，将各组大鼠肝左、中叶切除，余肝作不同处理：单纯肝切除组不阻断其血流；缺血组阻断血流30min后恢复灌注；后处理组阻断血流30min，并于恢复灌注前进行30s-30s循环3次后处理。术后1、6、12、24、48h取各组大鼠余肝组织，测定TNF—α、IL-6水平，STAT-3、细胞周期蛋白（cyclin）D1、Cdk4 mRNA表达及cyclinD1、Cdk4蛋白表达水平。结果与单纯肝切除组比较，缺血组各时点IL-6表达降低（t=5．076～8．334，P=0．000），TNF-α于1～12h明显升高（t=2．972～7．215，P=0．000～0．014），24h、48h的cyclinD1、Cdk4、STAT-3 mRNA及cyclinD1、Cdk4蛋白表达水平降低（t=2．857～6．684，P=0．000～0．017）。与缺血组比较，后处理组各时点IL-6表达水平升高（t=2．458～3．543，P=0．005～0．034），TNF—α于1～12h降低（t=2．995～4．112，P=0．002～0．017）；24h、48h的STAT-3、cyclinD1、Cdk4mRNA表达及cyclinD1、Cdk4蛋白表达水平（t=2．383—6．803，P=0．000～0．038）均升高。结论缺血后处理对肝大部切除合并缺血再灌注损伤余肝的再生具有促进作用，其机制与TNF-α／IL-6／STAT-3信号通路激活，促使肝细胞cyclinD1-Cdk4复合物产生，促进肝细胞增殖有关。
Objective To investigate the impact of the ischemic postconditioning on the tumor necrosis factor （TNF）-α/IL-6/signal transducers and activators of transcription （STAT）-3 signal pathway of liver regeneration. Methods Ninety healthy clean grade male Sprague-Dawley rats weighting 230 to 280 g were selected and assigned into three groups randomly ： group Ⅰ subtotal hepatectomy （ SH ） , group Ⅱ isehemia reperfusion （IR）, group Ⅲ ischemic postconditioning （IPO）. The left and middle liver was resected, and the remnant liver was treated as followed： the blood flow was not blocked in SH group, but blocked 30 minutes in IR group, then reperfused; IPO groups received three cycles of 30 s-30 s intermittent interruptions of blood flow at onset of reperfusion. At 1, 6, 12, 24, 48 h after reperfusion, the serum TNF-α, IL-6 was detected and the mRNA of cyclinD1, Cdk4, STAT-3 was assayed by real-time PCR as well as the protein expression of cyelinD1 and Cdk4 by Western blot. Results Compared with SH group, the expression of IL-6 declined at each set time point in IR group （ t = 5. 076 to 8. 334, P = 0. 000）, but the content of TNF-α increased in early stage （1 to 12 h） （t = 2.972 to 7.215, P =0.000-0.014）. Theexpression of STAT-3 ,cyclinD1 and Cdk4 mRNA and protein of cyclinDl and Cdk4 at 24 and 48 h after reperfusion were lower in [R group than in SH group （t = 2. 857 to 6. 684, P = 0. 000 to 0. 017 ）. However, there was a significant decrease in TNF-α from 1 to 12 h after reperfusion （ t = 2. 995 to 4. 112, P = 0. 002 to 0. 017）, but a significant increase in IL-6 in IPO group than in IR group （t =2. 458 to 3. 543, P =0. 005 to 0. 034）. The expression of STAT-3, cyclinD1, Cdk4 mRNA and protein of cyclinD1 and Cdk4 at 24 and 48 h after reperfusion were all increased in IPO group in comparison with in IR group （ t = 2. 383 to 6. 803, P = 0. 000 to 0. 038 ）. Conclusions The ischemic postconditioning could promote the remnant liver regeneration after subtotal hepatectomy with ischemia reperfusion injury. Its mechanism relates with the activation of the TNF-α/IL-6/STAT-3 signal pathway of and the cyclinD1-Cdk4 complex which enhances the proliferation of hepatoeyte.
出处
《中华外科杂志》
CAS
CSCD
北大核心
2012年第10期909-913,共5页
Chinese Journal of Surgery
基金
基金项目：陕西省科技攻关资助项目（2008K14-02）
关键词
缺血预处理
再灌注损伤
肝再生
肿瘤坏死因子Α
白细胞介素6
信号传导
STAT3转录因子
Isehemic preconditioning
Reperfusion injury
Liver regeneration
Tumornecrosis factor - alpha
Interleukin-6
Signal transduction
STAT3 transcription factor
