CAJ | 학술논문

目的研究肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)诱导肝细胞凋亡在暴发性肝衰竭中的作用机制。方法分别注射脂多糖(lipopolysaccharide, LPS) 和 TNF-α于 D-氨基半乳糖(D-galac-tosamine, GalN)致敏的BALB/c小鼠，造成暴发性肝衰竭模型，用脱氧核糖核酸转移酶介导的缺口原位末端标记 (in site end labeling, ISEL)技术、电镜及抽提肝组织DNA琼脂糖凝胶电泳检测DNA Ladder观察肝细胞凋亡，同时探索肝细胞凋亡和肝细胞坏死间的关系。结果 GalN/LPS和GalN/TNF-α组小鼠均发生肝细胞凋亡、坏死，最终因肝功能衰竭死亡。3．5 h～6 h肝细胞以凋亡为主，6 h以后则以坏死为主，直到小鼠死亡时肝细胞凋亡仍持续存在。预先使用抗TNF-α抗体可阻断GalN/LPS介导的肝细胞凋亡、坏死和小鼠死亡。结论 TNF-α是内毒素血症中造成肝细胞凋亡的终末介质，肝细胞凋亡存在于整个病程中，而坏死则在病程后期出现，凋亡的肝细胞可能引发了肝细胞坏死。
목적연구종류배사인자-α(tumor necrosis factor-α, TNF-α)유도간세포조망재폭발성간쇠갈중적작용궤제。방법분별주사지다당(lipopolysaccharide, LPS) 화 TNF-α우 D-안기반유당(D-galac-tosamine, GalN)치민적BALB/c소서，조성폭발성간쇠갈모형，용탈양핵당핵산전이매개도적결구원위말단표기 (in site end labeling, ISEL)기술、전경급추제간조직DNA경지당응효전영검측DNA Ladder관찰간세포조망，동시탐색간세포조망화간세포배사간적관계。결과 GalN/LPS화GalN/TNF-α조소서균발생간세포조망、배사，최종인간공능쇠갈사망。3．5 h～6 h간세포이조망위주，6 h이후칙이배사위주，직도소서사망시간세포조망잉지속존재。예선사용항TNF-α항체가조단GalN/LPS개도적간세포조망、배사화소서사망。결론 TNF-α시내독소혈증중조성간세포조망적종말개질，간세포조망존재우정개병정중，이배사칙재병정후기출현，조망적간세포가능인발료간세포배사。
Objective To study the roles of tumor necrosis factor-α (TNF-α) induced hepatocyte apop-tosis in the development of fulminant liver failure (FLF). Methods Liver damage was induced by TNF-α or lipopolysaccharide (LPS) in D-galactosamine (GalN) sensitized BALB/c mice. Morphologic and biological changes of hepatocyte apoptosis were studied by light microscopy, electron microscopy, in site end labeling (ISEL) and DNA ladder detection. Results Both GalN + LPS and GalN + TNF-a induced hepatocyte apop-tosis and necrosis, and finally resulted in liver failure. Hepatocyte apoptosis was observed at 3.5、 6 hours after treatment with GalN + LPS or GalN + TNF-α, hepatocyte necrosis was not remark at this time but obvious at 9 hours. In the field of necrosis, there was inflammatory cell infiltration. Hepatocyte apoptosis was observed in whole course till the mice death. Administration of GalN、 LPS or TNF-α alone, didn't induce apoptosis or necrosis. Pretreatment with anti-TNF-α IgG1 completely inhibited the liver injure caused by GalN + LPS.Conclusions The TNF-α is the last one factor and plays a causal role in LPS-induced hepatic apoptosis、necrosis and liver failure.