NF-κB对肠缺血再灌注肝损伤P-选择素表达和中性粒细胞浸润的作用  

Effect of nuclear factor-κB on P-selectin expression and neutrophil infiltration in liver injury induced by intestinal ischemia/reperfusion in rats

作　　者：李英华[1] 田晓峰[1] 王真真[2] 张雪松[3] 张峰[2] 金松[2] 姚继红[2] 

机构地区：[1]大连医科大学附属第二医院普外科辽宁省大连市,116023 [2]大连医科大学药理教研室,辽宁省大连市116027 [3]大连医科大学附属第二医院普外科,辽宁省大连市116023

出　　处：《世界华人消化杂志》2006年第5期486-490,共5页World Chinese Journal of Digestology

基　　金：辽宁省科学技术厅自然科学基金资助项目;No.20042135~~

摘　　要：目的:探讨核转移因子-κB(NF-κB)在肠缺血再灌注肝损伤发病机制中的作用及其对P-选择素(P-selectin)表达和中性粒细胞浸润的影响．方法:Wistar大鼠24只随机分成对照(Control 组)、肠缺血再灌注(I／R组)和脯氨酸二硫代氨基甲酸酯(PDTC)治疗组(PDTC组),每组8只．I／ R和PDTC组大鼠行肠系膜上动脉夹闭1 h再灌注2 h．PDTC组于手术前1 h给予20 g／L PDTC 100 mg／kg ip．观察肝组织病理学及其肝功能变化,检测血清IL-6,肝组织匀浆超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)水平．免疫组化法观察肝组织P-selectin和NF-κB表达并采用Western blot法检测肝NF-κB的水平．结果:肠缺血再灌注诱发了肝损伤,表现为肝水肿、出血和炎性粒细胞浸润．与对照组相比,I／R组血清ALT、AST、IL-6水平明显升高 (143．16±53．02至192．31±42．09 U／L,P<0．05; 387．46±78．74至507．56±96．26 U／L,P<0．01; 22．51±6．10至42．85±7．35 ng／L,P<0．01)．肝组织SOD活性降低、MPO含量明显升高(244．87 ±25．11至173．21±16．60 U／mgprot,P<0．01; 2．36±0．56至4.32±0．77 U／g,P<0．01);肝组织的P-selectin和NF-κB表达增强．采用PDTC 预处理,与I／R组相比,肝损伤程度减轻,血清ALT(128．63±38．94 U／L)、AST(462．86± 60．84 U／L)以及IL-6(28．08±7．55 ng／L)水平明显降低(P<0．01,P<0．05,P<0．05);肝脏氧化损伤及白细胞浸润减弱,表现为肝组织SOD活性升高(253．45±25．21 U／mgprot,P<0．01)、MPO 含量降低(3．58±0．49 U／g,P<0．05),同时伴有肝组织中的P-selectin和NF-κB表达减弱．结论:肠缺血再灌注诱发肝损伤,伴有明显的中性粒细胞浸润和肝组织P-selectin的表达增强,NF-κB的活化在此损伤过程中起重要作用． PDTC通过抑制NF-κB活性对肠缺血再灌注肝损伤起保护作用．AIM： To investigate the effect of nuclear factor-κB （NF-κB） on P-selectin expression and neutrophil accumulation in liver injury induced by intestinal ischemia/reperfusion （I/R） in rats. METHODS： Twenty-four Wistar rats were randomly assigned into sham operation （control, n = 8）, intestinal I/R （n = 8）, and pyrrolidine dithiocarbamate （PDTC） treatment （n = 8）. The rats in I/R and PDTC group received 1 h SMA occlusion and 2 h reperfusion, and those in PDTC group was also intraperitoneally injected with 20 g/L PDTC （100 mg/kg） I h before operation.Liver histology was observed under light micro-scope. The level of serum alanine aminotransferse （ALT）, aspartate aminotransferase （AST） andinterleukin-6 （IL-6）, and liver tissue superoxidedismutase （SOD）, myeloperoxidase （MPO） con-tents were measured. The immunohistochemicalexpression of liver NF-κB and P-selectin as well asWestern blot analysis of liver NF-κB were assayed.RESULTS： Liver injury was induced by intesti-nal I/R, characterized as histological damage ofedema, hemorrhage and polymorphonuclear iniltration as well as the significant rise of serum ALT （from 143.16 ± 53.02 to 192.31 ± 42.09 U/L,P 〈 0.05） and ABT level （from 387.46 ± 78.74 to507.56 ± 96.26 U/L, P 〈 0.01）. In comparison withthat in control group, the level of serum IL-6 in-creased significantly （from 22.51 ± 6.10 to 42.85±7.35 ng/L, P 〈 0.01） in I/R group, and tissue SOD decreased （from 244.87 ± 25.11 to 173.21±16.60 U/mgprot, P 〈 0.01） while while MPO increased （from 2.36 ± 0.56 to 4.32 ± 0.77 U/g, P 〈 0.01） sig-rdficanfly. Strong positive expression of NF-κB p65 and P-selectin were observed. After PDTCadministration, the level of serum IL-6, tissueSOD and MPO were improved markedly （28.08± 7.55 ng/L, P 〈 0.05; 253.45 ± 25.21 U/mgprot,P 〈 0.01; 3.58 ± 0.49 U/g, P 〈 0.05） as comparedwith those in I/R group, and the expression of NF-κB and P-selectin were weakened markedly. CONCLUSION�

关 键 词：肝损伤 肠缺血再灌注 核转录因子ΚB P-选择素 

分 类 号：R574[医药卫生—消化系统]