中华实验外科杂志
中華實驗外科雜誌
중화실험외과잡지
CHINESE JOURNAL OF EXPERIMENTAL SURGERY
2013年
2期
285-287
,共3页
马毅%胡斌%黄凯军%汪荣%程东辉
馬毅%鬍斌%黃凱軍%汪榮%程東輝
마의%호빈%황개군%왕영%정동휘
细胞因子信号转导抑制因子-1%急性肝损伤%内毒素耐受
細胞因子信號轉導抑製因子-1%急性肝損傷%內毒素耐受
세포인자신호전도억제인자-1%급성간손상%내독소내수
Suppressors of cytokine signaling-1%Acute liver injury%Endotoxin tolerance
目的 观察细胞因子信号转导抑制因子1(SOCS-1)在内毒素-脂多糖(LPS)诱导小鼠急性肝损伤中肝组织的表达变化,探讨SOCS-1调控肝脏免疫炎性损伤作用的可能机制.方法 72只雄性BALB/c小鼠随机分为以下3组,每组24只小鼠.A组:急性肝损伤模型组(ALI组),半乳糖胺(D-GaIN)溶于无菌0.9％氯化钠注射液,用1 mol氢氧化钠调至pH 7.0,与LPS同时腹腔注射,所用D-GaIN和LPS剂量分别为0.02μg/只和4.00 μg/只；B组:内毒素耐受组(ETT组),LPS溶于无菌0.9％氯化钠注射液,以0.002 μg/kg小剂量腹腔注射,1次/d,连续5次,于LPS第5次注射24h后腹腔注射D-GaIN/LPS,剂量和处理与ALI组相同；C组:正常对照组,腹腔注射0.9％氯化钠注射液0.2ml.上述各实验组小鼠分别于注射D-GaIN/LPS或0.9％氯化钠注射液6、12、24h后的3个时间点留取小鼠血及肝脏标本.观察肝组织病理变化；检测小鼠肝组织中SOCS-1 mRNA和蛋白的表达；同时检测血清肿瘤坏死因子(TNF)-α以及血清氨酸氨基转移酶(ALT)和总胆红素(TBiL)水平.结果 ALI组肝组织可见大片肝细胞变性、坏死以及汇管区有较多的炎性细胞浸润等病理改变,ALI组小鼠肝组织SOCS-1 mRNA和蛋白的表达均明显上调,造模后6h即明显高于正常对照组,且分别于12 h达到高峰(P＜0.05)；ETT组的肝组织病理改变明显轻于ALI组,其血清TNF-α、ALT、TBiL水平明显低于ALI组(P＜0.05),而ETT组的SOCS-1 mRNA和蛋白的表达则较ALI组上升更为明显(P＜0.05).结论 LPS导致的小鼠ALI可诱导SOCS-1在肝组织的表达增多；内毒素耐受时,对其后大剂量LPS的再次刺激而引起肝脏损害减轻、TNF-α释放减少,则可能与肝组织SOCS-1进一步高表达有关；该研究提示SOCS-1在调控肝脏免疫炎性损伤中可能具有抗损伤作用.
目的 觀察細胞因子信號轉導抑製因子1(SOCS-1)在內毒素-脂多糖(LPS)誘導小鼠急性肝損傷中肝組織的錶達變化,探討SOCS-1調控肝髒免疫炎性損傷作用的可能機製.方法 72隻雄性BALB/c小鼠隨機分為以下3組,每組24隻小鼠.A組:急性肝損傷模型組(ALI組),半乳糖胺(D-GaIN)溶于無菌0.9％氯化鈉註射液,用1 mol氫氧化鈉調至pH 7.0,與LPS同時腹腔註射,所用D-GaIN和LPS劑量分彆為0.02μg/隻和4.00 μg/隻；B組:內毒素耐受組(ETT組),LPS溶于無菌0.9％氯化鈉註射液,以0.002 μg/kg小劑量腹腔註射,1次/d,連續5次,于LPS第5次註射24h後腹腔註射D-GaIN/LPS,劑量和處理與ALI組相同；C組:正常對照組,腹腔註射0.9％氯化鈉註射液0.2ml.上述各實驗組小鼠分彆于註射D-GaIN/LPS或0.9％氯化鈉註射液6、12、24h後的3箇時間點留取小鼠血及肝髒標本.觀察肝組織病理變化；檢測小鼠肝組織中SOCS-1 mRNA和蛋白的錶達；同時檢測血清腫瘤壞死因子(TNF)-α以及血清氨痠氨基轉移酶(ALT)和總膽紅素(TBiL)水平.結果 ALI組肝組織可見大片肝細胞變性、壞死以及彙管區有較多的炎性細胞浸潤等病理改變,ALI組小鼠肝組織SOCS-1 mRNA和蛋白的錶達均明顯上調,造模後6h即明顯高于正常對照組,且分彆于12 h達到高峰(P＜0.05)；ETT組的肝組織病理改變明顯輕于ALI組,其血清TNF-α、ALT、TBiL水平明顯低于ALI組(P＜0.05),而ETT組的SOCS-1 mRNA和蛋白的錶達則較ALI組上升更為明顯(P＜0.05).結論 LPS導緻的小鼠ALI可誘導SOCS-1在肝組織的錶達增多；內毒素耐受時,對其後大劑量LPS的再次刺激而引起肝髒損害減輕、TNF-α釋放減少,則可能與肝組織SOCS-1進一步高錶達有關；該研究提示SOCS-1在調控肝髒免疫炎性損傷中可能具有抗損傷作用.
목적 관찰세포인자신호전도억제인자1(SOCS-1)재내독소-지다당(LPS)유도소서급성간손상중간조직적표체변화,탐토SOCS-1조공간장면역염성손상작용적가능궤제.방법 72지웅성BALB/c소서수궤분위이하3조,매조24지소서.A조:급성간손상모형조(ALI조),반유당알(D-GaIN)용우무균0.9％록화납주사액,용1 mol경양화납조지pH 7.0,여LPS동시복강주사,소용D-GaIN화LPS제량분별위0.02μg/지화4.00 μg/지；B조:내독소내수조(ETT조),LPS용우무균0.9％록화납주사액,이0.002 μg/kg소제량복강주사,1차/d,련속5차,우LPS제5차주사24h후복강주사D-GaIN/LPS,제량화처리여ALI조상동；C조:정상대조조,복강주사0.9％록화납주사액0.2ml.상술각실험조소서분별우주사D-GaIN/LPS혹0.9％록화납주사액6、12、24h후적3개시간점류취소서혈급간장표본.관찰간조직병리변화；검측소서간조직중SOCS-1 mRNA화단백적표체；동시검측혈청종류배사인자(TNF)-α이급혈청안산안기전이매(ALT)화총담홍소(TBiL)수평.결과 ALI조간조직가견대편간세포변성、배사이급회관구유교다적염성세포침윤등병리개변,ALI조소서간조직SOCS-1 mRNA화단백적표체균명현상조,조모후6h즉명현고우정상대조조,차분별우12 h체도고봉(P＜0.05)；ETT조적간조직병리개변명현경우ALI조,기혈청TNF-α、ALT、TBiL수평명현저우ALI조(P＜0.05),이ETT조적SOCS-1 mRNA화단백적표체칙교ALI조상승경위명현(P＜0.05).결론 LPS도치적소서ALI가유도SOCS-1재간조직적표체증다；내독소내수시,대기후대제량LPS적재차자격이인기간장손해감경、TNF-α석방감소,칙가능여간조직SOCS-1진일보고표체유관；해연구제시SOCS-1재조공간장면역염성손상중가능구유항손상작용.
Objective To observe the expression change of suppressors of cytokine signaling-1 (SOCS-1) in acute lver injury (ALI) induced by endotoxin-lipopolysaccharide (LPS),and investigate the probable mechanism of SOCS-1 regulating immune inflammatory injury in the liver.Methods Seventytwo male BALB/c mice were randomized into 3 groups (n =24 each).Group A,ALI group:D-galactosamine (D-GaIN) was dissolved in 0.9％ aseptic sodium chloride injection.Mter adjusting the pH to 7.0 with sodium hydroxide,the mixture was injected intraperitoneally with LPS.The dosage of D-GaIN and LPS was 0.02 μg/kg and 4.00 μg/kg,respectively; Group B,endotoxin tolerance group (ETF group):LPS was dissolved in 0.9％ aseptic sodium chloride injection.Intraperitoneal injection was then performed at the low dose of 0.002 μg/kg,once daily for 5 days.Intraperitoneal injection of D-GaIN/LPS was performed 24 h after the fifth injection of LPS.All the processes and dosages were similar to ALI group; Group C,control group:only intraperitoneal injection of 0.2 ml 0.9％ aseptic sodium chloride injection was performed.Blood and liver specimens were obtained from mice in all groups at 6,12 and 24 h after the injection of D-GaIN/LPS or 0.9％ aseptic sodium chloride.The pathological changes of the liver were observed and the expression of SOCS-1 mRNA and protein in the liver of mice as well as serum tumor necrosis factor-α(TNF-α),alanine aminotransferase (ALT) and total bilirubin (TBiL) levels were detected.Results Large area of liver cell degeneration,necrosis and numerous inflammation cell infiltration were found in portal area in ALI group.SOCS-1 mRNA and protein expression in the liver of mice was increased significantly in ALI group,as compared with control group 6 h after modeling,and reached the peak at 12 h (P ＜ 0.05).Pathological changes in the liver were significantly milder in ETI group than in ALI group.Serum TNF-α,ALT and TBiL levels were significantly lower in ETI group than in ALI group (P ＜ 0.05).The expression of SOCS-1 mRNA and protein in the liver was increased even more significantly in ETT group than in ALI group.Conclusion ALI induced by LPS can result in the increased expression of SOCS-1 in the liver.The liver injury and TNF-α release caused by high dose of LPS re-stimulation will be decreased when endotoxin tolerated,and this may be associated with further increased expression of SOCS-1.This research demonstrated that SOCS-1 may have anti-injury effect on regulating liver immune inflammatory injury.
