CAJ | 학술논문

目的探讨NF-κB对重症急性胰腺炎(SAP)大鼠炎症因子TNF-α、IL-1β和sICAM-1的调控作用及其早期的动态变化及意义,并观察吗替麦考酚酯(mycophenolate mofetil,MMF)的干预性作用.方法将104只雄性Wistar大鼠随机(随机数字法)分成健康组、假手术组、SAP组、MMF组.(1)健康组仅开腹后缝合即可(n=8)；(2)假手术组开腹后仅翻动胰腺并以钝器轻划胰腺组织5次(n=32)；(3) SAP组采用逆行胰胆管注射牛黄胆酸钠法建立SAP模型(n=32)；(4) MMF组大鼠在完成SAP模型后1h经尾静脉注射MMF 250 mg/kg(n=32).于造模后3、6、12、24 h时点分批处死大鼠,常规HE染色进行胰腺组织病理评分；采用全自动生化分析仪检测血清淀粉酶AMS、血清C反应蛋白(CRP)；ELISA法检测血清TNF-α、IL-1β和sICAM-1的含量；荧光定量PCR法检测胰腺组织NF-κB mRNA表达.结果 SAP组与健康组、假手术组比较,胰腺组织病理评分与血清AMS、CRP、TNF-α、IL-1β及sICAM-1的含量、胰腺组织NF-κB mRNA表达在各时间点均显著升高(P＜0.05),干预组使用MMF后,胰腺组织病理评分、血清AMS、CRP、TNF-α、IL-1β和sICAM-1水平、胰腺组织NF-κB mRNA同SAP组相比均有明显降低(P＜0.05).结论 SAP早期阶段细胞因子的变化与SAP病情进展密切相关,MMF可通过抑制细胞免疫及炎性细胞因子的产生,减轻炎症损伤反应.
목적 탐토NF-κB대중증급성이선염(SAP)대서염증인자TNF-α、IL-1β화sICAM-1적조공작용급기조기적동태변화급의의,병관찰마체맥고분지(mycophenolate mofetil,MMF)적간예성작용.방법 장104지웅성Wistar대서수궤(수궤수자법)분성건강조、가수술조、SAP조、MMF조.(1)건강조부개복후봉합즉가(n=8)；(2)가수술조개복후부번동이선병이둔기경화이선조직5차(n=32)；(3) SAP조채용역행이담관주사우황담산납법건립SAP모형(n=32)；(4) MMF조대서재완성SAP모형후1h경미정맥주사MMF 250 mg/kg(n=32).우조모후3、6、12、24 h시점분비처사대서,상규HE염색진행이선조직병리평분；채용전자동생화분석의검측혈청정분매AMS、혈청C반응단백(CRP)；ELISA법검측혈청TNF-α、IL-1β화sICAM-1적함량；형광정량PCR법검측이선조직NF-κB mRNA표체.결과 SAP조여건강조、가수술조비교,이선조직병리평분여혈청AMS、CRP、TNF-α、IL-1β급sICAM-1적함량、이선조직NF-κB mRNA표체재각시간점균현저승고(P＜0.05),간예조사용MMF후,이선조직병리평분、혈청AMS、CRP、TNF-α、IL-1β화sICAM-1수평、이선조직NF-κB mRNA동SAP조상비균유명현강저(P＜0.05).결론 SAP조기계단세포인자적변화여SAP병정진전밀절상관,MMF가통과억제세포면역급염성세포인자적산생,감경염증손상반응.
Objective To observe the modulatory effects of NF-κB on dynamic changes of TNF-α、IL-1β and ICAM-1 in rats with severe acute pancreatitis (SAP),and to assess the effects of pretreatment with mycophenolate mofetil (MMF) on them.Methods A total of 104 male Wistar rats were randomly divided into normal group,sham operation group,SAP group and MMF group.(1) In normal group,rats had just an incision on abdomen wall and sutured (n =8) ; (2) In sham operation group,rats underwent laparotomy with flipping over the pancreas and gendy striking five times by using blunt instrument and abdomen was closed (n =32); (3) In SAP group,SAP in rats was induced by the retrograde injection of sodium taurocholate (STC) into the pancreatic duct (n =32) ; (4) In MMF group,MMF (250mg/kg)was injected intraperitoneally one hours after injection of STC (n =32).Rats were saerificed by abdominalaorta exsanguination separately at intervals of 3,6,12 and 24 h after modeling of pancreatitis.Histologic score of pancreatic tissue was assessed,and serum amylase (AMS) and serum C-reactive protein (CRP)were measured by automatic biochemical detector.The serum levels of inflammatory cyctokines (TNF-α,1L-1β and 1CAM-1 ) were measured by using ELISA,and expression of NF-κB mRNA in pancreatic tissue was measured by using quantitative PCR.Results Compared with sham operation group,histologic score of pancreatic tissue,serum amylase,TNF-α、IL-1β and ICAM-1 in SAP group were increased significantly (P ＜ 0.05 ).Pretreatment with MMF obviously deceased histologic score,and the serum levels of amylase,TNF-α,IL-1β and ICAM-1 and the expression of NF-κB mRNA were higher than those in SAP group in early stage (P ＜0.05 ).Conclusions Cytokines play an important role in early stage of SAP.MMF could attenuate the severity of inflammatory response through inhibiting cellular immunity and modulating the proinflammatory cytokines produced.