中华急诊医学杂志
中華急診醫學雜誌
중화급진의학잡지
CHINESE JOURNAL OF EMERGENCY MEDICINE
2013年
2期
148-152
,共5页
温韬%勾春燕%卢静%刘焱%朴正福%李峰%陈德喜
溫韜%勾春燕%盧靜%劉焱%樸正福%李峰%陳德喜
온도%구춘연%로정%류염%박정복%리봉%진덕희
细胞外组蛋白%肝衰竭%细胞凋亡%中和抗体%炎症%肿瘤坏死因子-α
細胞外組蛋白%肝衰竭%細胞凋亡%中和抗體%炎癥%腫瘤壞死因子-α
세포외조단백%간쇠갈%세포조망%중화항체%염증%종류배사인자-α
Extracellular histones%Acute liver failure%Cell apoptosis%Neutralizing antibody%Inflammation%TNF-α
目的 研究急性肝衰竭小鼠细胞外组蛋白的水平变化及干预价值.方法 选野生型C57BL/6小鼠,经腹腔注射致死剂量的D-氨基半乳糖和脂多糖诱导急性肝衰竭,动态测定血浆中细胞外组蛋白的水平以及肝功能、细胞凋亡等指标；分别给予特异性抗组蛋白H3和H4中和抗体进行干预,并检测小鼠生存率和肝损伤指标以及肿瘤坏死因子TNF-α水平等.结果 D-氨基半乳糖和脂多糖联用导致小鼠急性肝衰竭,表现为血浆ALT水平明显升高,大量肝细胞凋亡和坏死,所有小鼠于9～12h内死亡；染毒后小鼠细胞外组蛋白水平呈时间依赖方式明显增高,和对照组相比差异具有统计学意义(P＜0.01).染毒小鼠分别经特异性抗组蛋白中和抗体H3和H4干预后,病死率明显下降(P =0.037,P=0.025),其机制可能与抑制TNF-α水平有关.结论 细胞外组蛋白是肝衰竭发病过程中的重要炎性介质,以细胞外组蛋白为靶点进行干预可能是今后重型肝炎治疗的新策略,值得深入探讨.
目的 研究急性肝衰竭小鼠細胞外組蛋白的水平變化及榦預價值.方法 選野生型C57BL/6小鼠,經腹腔註射緻死劑量的D-氨基半乳糖和脂多糖誘導急性肝衰竭,動態測定血漿中細胞外組蛋白的水平以及肝功能、細胞凋亡等指標；分彆給予特異性抗組蛋白H3和H4中和抗體進行榦預,併檢測小鼠生存率和肝損傷指標以及腫瘤壞死因子TNF-α水平等.結果 D-氨基半乳糖和脂多糖聯用導緻小鼠急性肝衰竭,錶現為血漿ALT水平明顯升高,大量肝細胞凋亡和壞死,所有小鼠于9～12h內死亡；染毒後小鼠細胞外組蛋白水平呈時間依賴方式明顯增高,和對照組相比差異具有統計學意義(P＜0.01).染毒小鼠分彆經特異性抗組蛋白中和抗體H3和H4榦預後,病死率明顯下降(P =0.037,P=0.025),其機製可能與抑製TNF-α水平有關.結論 細胞外組蛋白是肝衰竭髮病過程中的重要炎性介質,以細胞外組蛋白為靶點進行榦預可能是今後重型肝炎治療的新策略,值得深入探討.
목적 연구급성간쇠갈소서세포외조단백적수평변화급간예개치.방법 선야생형C57BL/6소서,경복강주사치사제량적D-안기반유당화지다당유도급성간쇠갈,동태측정혈장중세포외조단백적수평이급간공능、세포조망등지표；분별급여특이성항조단백H3화H4중화항체진행간예,병검측소서생존솔화간손상지표이급종류배사인자TNF-α수평등.결과 D-안기반유당화지다당련용도치소서급성간쇠갈,표현위혈장ALT수평명현승고,대량간세포조망화배사,소유소서우9～12h내사망；염독후소서세포외조단백수평정시간의뢰방식명현증고,화대조조상비차이구유통계학의의(P＜0.01).염독소서분별경특이성항조단백중화항체H3화H4간예후,병사솔명현하강(P =0.037,P=0.025),기궤제가능여억제TNF-α수평유관.결론 세포외조단백시간쇠갈발병과정중적중요염성개질,이세포외조단백위파점진행간예가능시금후중형간염치료적신책략,치득심입탐토.
Objective To investigate the changes of extracellular histones during the course of acute liver failure in mice as well as its therapeutic potential.Methods WT mice (C57BL/6) were randomly (random number) allocated to inducing acute liver failure by lethal doses of GalN/LPS injected i.p.Hepatic function,apoptosis of hepatocytes and histological indexes were measured at different intervals following GalN/LPS challenge.The levels of extracellular histones were determined by using ELISA and Western blot methods.Meanwhile,GalN/LPS-treated mice were administered with anti-histone H3 and antihistone H4 neutralized antibodies,respectively.Results Administration of GalN/LPS to mice caused acute liver failure,characterized by significant elevation of plasma ALT levels and massive hepatocyte apoptosis or necrosis.All mice died within 9-12 hours.The levels of nucleosomes and extracellular histones H3 and H4 were increased considerably in a time-dependent manner.The survival rates in GalN/LPS-treated mice were improved remarkably following administration of anti-histone H3 and H4 neutralized antibodies (P =0.037,P =0.025),likely due to the significant inhibition of TNF-production.Conclusions Extracellular histones are an important mediator implicated in the pathogenesis of acute liver failure.Anti-histones show promising potential in the treatment of acute liver failure,which deserves further investigation in the future.
