CAJ | 학술논문

目的通过研究内毒素耐受(endotoxin tolerance,ETT)对急性肝功能衰竭(acute liver failure,ALF)大鼠肝组织中趋化因子受体7(chemokine receptor 7,CXCR7)表达变化的影响,探讨ETT发生的可能机制.方法雄性SD大鼠随机(随机数字法)分为健康对照组(N组)、急性肝功能衰竭组(ALF组)和内毒素耐受组(ETF组).ETT组和ALF组先分别以0.1mg/kg脂多糖(lipopoIysaccharide,LPS)和生理盐水腹腔注射,每日1次,于第5次注射24 h后同时腹腔注射D-氨基半乳糖(D-galactosamine,D-GalN) (800 mg/kg)和LPS(8μg/只),分别在注射后2、6、12、24、48 h时间点留取大鼠血及肝脏标本.RT-PCR法检测肝组织中CXCR7mRNA表达；Western blot法检测CXCR7蛋白表达.统计处理采用LSD检验、Dunnet's t检验.结果 ETT组大鼠肝组织病理改变较ALF组明显减轻；ETT组肝组织CXCR7mRNA表达水平虽高于正常组,但却明显低于ALF组,与ALF组比较,差异均具有统计学意义(2、6、12、24、48 h时间点比较,F值分别为29.222、166.892、38.975、34.603、18.929,均P＜0.01).ETT组、ALF组CXCR7蛋白的表达24 h时均达峰值,但ETT组CXCR7蛋白的表达较ALF组明显下降(2、6、12 h时的F值分别为11.155、42.553、17.082,均P＜0.01；24 h时的F值7.242,P＜0.05).结论内毒素耐受时,大剂量LPS和D-GalN能减轻肝脏损害,明显下调CXCR7mRNA和CXCR7蛋白表达,提示CXCR7在内毒素耐受的形成机制中可能发挥重要作用.
목적 통과연구내독소내수(endotoxin tolerance,ETT)대급성간공능쇠갈(acute liver failure,ALF)대서간조직중추화인자수체7(chemokine receptor 7,CXCR7)표체변화적영향,탐토ETT발생적가능궤제.방법 웅성SD대서수궤(수궤수자법)분위건강대조조(N조)、급성간공능쇠갈조(ALF조)화내독소내수조(ETF조).ETT조화ALF조선분별이0.1mg/kg지다당(lipopoIysaccharide,LPS)화생리염수복강주사,매일1차,우제5차주사24 h후동시복강주사D-안기반유당(D-galactosamine,D-GalN) (800 mg/kg)화LPS(8μg/지),분별재주사후2、6、12、24、48 h시간점류취대서혈급간장표본.RT-PCR법검측간조직중CXCR7mRNA표체；Western blot법검측CXCR7단백표체.통계처리채용LSD검험、Dunnet's t검험.결과 ETT조대서간조직병리개변교ALF조명현감경；ETT조간조직CXCR7mRNA표체수평수고우정상조,단각명현저우ALF조,여ALF조비교,차이균구유통계학의의(2、6、12、24、48 h시간점비교,F치분별위29.222、166.892、38.975、34.603、18.929,균P＜0.01).ETT조、ALF조CXCR7단백적표체24 h시균체봉치,단ETT조CXCR7단백적표체교ALF조명현하강(2、6、12 h시적F치분별위11.155、42.553、17.082,균P＜0.01；24 h시적F치7.242,P＜0.05).결론 내독소내수시,대제량LPS화D-GalN능감경간장손해,명현하조CXCR7mRNA화CXCR7단백표체,제시CXCR7재내독소내수적형성궤제중가능발휘중요작용.
Objective To study the effect of endotoxin tolerance (ETT) on chemokine receptor 7 (CXCR7) in the liver tissue of rats with acute liver failure (ALF).Methods SD male rats were randomly divided into three groups:normal group,ALF group and ETT group.The rats in the ETT group and ALF group were injected with lipopolysacharide (LPS) 0.1 mg/kg or saline respectively,one time / day for 5 days.At 24 hours after the 5th-day injection,all rats were injected with D-GalN 800 mg/kg and LPS 8μg/rat.Blood sample and liver tissue were collected on 2,6,12,24 and 48 hours after injection.The gene expressions of CXCR7 in the liver were measured by RT-PCR,and the protein expressions of CXCR7 were determined by Western Blot.The data analysis was performed by LSD,Dunnett's t test.Results The histological damage in the liver tissue was significantly mider in ETT group compared to ALF group.The gene expressions of CXCR7 were significantly milder in ETT group compared to ALF group (2 h:F =29.222,6 h:F=166.892,12 h:F=38.975,24h:F=34.603,48 h:F=18.929,allP＜0.01),but still severer than that of normal group.The CXCR7 protein expression in ALF group and ETT group peaked at 24 hours,but the expression of CXCR7 in ETT group was lower compared with that in in ALF group (2h:F=11.155,6 h:F=42.553,12h:F=17.082,all P＜0.01; 24 h:F=7.242,P＜0.05).Conclusions During the process of endotoxin tolerance,LPS pretreatment and D-GalN can decrease the liver injury,down-regulate the expressions of CXCR7mRNA and CXCR7.This suggests that CXCR7 may play an important role in the ETT.