跨膜型和分泌型TNF-α在内毒素性休克过程中的作用  

The roles of mTNF-α and sTNF-α in endotoxin shock

作　　者：尹丙姣[1] 李卓娅[1] 余上斌[2] 姜晓丹[1] 龚非力[1] 徐勇[1] 冯玮[1] 熊平[1] 

机构地区：[1]华中科技大学同济医学院免疫学教研室,武汉430030 [2]华中科技大学同济医学院机能学实验中心

出　　处：《中华微生物学和免疫学杂志》2002年第3期334-338,共5页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金资助项目 (39630 32 0 )

摘　　要：目的　研究跨膜型TNF α(mTNF α)的消长与内毒素性休克发生、发展的关系 ,探讨mTNF α在内毒素性休克中的作用和机理。方法　首先使用埃希大肠杆菌死菌液制备大鼠内毒素性休克模型 ,并分不同时间点检测血清中的分泌型TNF α(sTNF α)、腹腔巨噬细胞表面上的mTNF α。然后 ,在给大鼠注射死菌液之前 30min ,分别注射TNF转化酶 (TACE)反义寡核甘酸 (5mg/kg)或抗TNF α多克隆抗体 (5mg/kg)。 6h后分别检测sTNF α、mTNF α水平 ;检查肺、肾等内脏器官的病理改变 ;并且监测各组大鼠的血压变化。结果　在内毒素性休克过程中 ,mTNF α表达的动态变化不同于sTNF α ,mTNF α在注射菌液 30min后开始升高 ,4 .5h达最高峰 ,随后有所下降 ,但一直维持在较高水平。TACE反义寡核苷酸能有效地抑制mTNF α转化为sTNF α ,使腹腔巨噬细胞表面上的mTNF α表达明显增高 (P <0 .0 0 1) ,使血压维持在正常水平 ,肺、肾等脏器无病理改变 ;抗TNF α多克隆抗体能中和sTNF α,其结果与前者基本相似。结论　内毒素性休克的病理过程主要与sTNF α及其诱导的其它促炎细胞因子如IL 1β、IL 6、IL 8等有关 ,而mTNF α则可抵抗内毒素的攻击 ,稳定血压 ,限制炎症反应及保护组织免受损伤 ,为临床治疗休克和感染性疾病提供了新的线索和实?Objective To observe the dynamic expression of mTNF α and sTNF α in the development of endotoxin shock and to explore the mechanism of mTNF α in endotoxin shock. Methods Endotoxin shock was induced in rats by intravenous injection of dead gram negative bacteria E.coli ; the kinetics of mTNF α in peritoneal macrophages and sTNF α in serum of these rats were examined. The pretreatment with TACE antisense oligodeoxyribonucleotide(TACE A ODN) (5mg/kg weight) or with polyclonal antibody against TNF α (5mg/kg weight) 30 minutes before injection of dead bacteria inhibited the enzymatic cleavage of mTNF α into sTNF α or neutralizated sTNF α. Six hours after bacteria injection, mTNF α and sTNF α also respectively detected. Pathological injury in lung and kidney in endotoxin shock rats was examined and arteria pressure was measured incessantly. Results The kinetics of mTNF α expression in the development of endotoxin shock was different from that of sTNF α in serum. The expression of mTNF α began to enhance on the surface of peritoneal macrophages in 30 min after the challenge of bacteria and reached the peak within a period of 4.5 hours followed by a gradual decrease to a certain level which was maintained at least 24 hours. TACE A ODN pretreated rats showed a markable increase in mTNF α expression by peritoneal macrophages ( P <0.001) and their arterial blood pressure were maintained in the normal rang and no detectable pathological injury was found in lung and kidney. Pretreat with polyclonal antibody against TNF α led to the similar results with that of the former. Conclusion mTNF α is a potential endogenous regulator involved in antiinflammatory responses to maintain the normal arterial pressure and protect tissue from pathological injury in the process of endotoxin shock. We demonstrated the kinetics of mTNF α expression and its potential effects in endotoxin shock were also reported. [

关 键 词：跨膜型TNF-Α 分泌型TNF-Α 内毒素性休克 TACE反义寡核苷酸 抗TNF多克隆抗体 

分 类 号：R363[医药卫生—病理学]