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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 investigate the relationship between the growth and decline of trans-membrane TNFα (mTNF α) and endotoxic shock and to explore the role and mechanism of mTNF α in endotoxic shock. Methods Endotoxic shock model of rat was made by using Escherichia coli dead bacteria liquid. Secretion type TNFα (sTNFα) and mTNFα in peritoneal macrophage were detected at different time points. Then, TNF converting enzyme (TACE) antisense oligonucleotide (5 mg / kg) or anti-TNF α polyclonal antibody (5 mg / kg) was injected respectively 30 min before the instillation of the dead bacteria into the rats. Six hours later, the levels of sTNF α and mTNF α were detected. The pathological changes of lung and kidney were detected. The changes of blood pressure in each group were also monitored. Results During the process of endotoxic shock, the dynamic changes of mTNFα expression was different from that of sTNFα. The mTNFα began to increase 30 min after the injection of bacterial liquid, reached the peak at 4.5 h, then decreased but maintained at a higher level Level. TACE antisense oligonucleotide can effectively inhibit the conversion of mTNF α to sTNF α, and significantly increase the expression of mTNF α on the peritoneal macrophages (P <0.01), maintain the normal blood pressure, Kidney and other organs without pathological changes; anti-TNF α polyclonal antibody can neutralize sTNF α, the results are basically similar with the former. Conclusions The pathological process of endotoxic shock is mainly related to sTNF α and other proinflammatory cytokines such as IL 1β, IL 6 and IL 8 induced by endotoxin shock. However, mTNF α can resist endotoxin attack, stabilize blood pressure and limit inflammation And protecting tissues from damage, providing new clues to the clinical treatment of shock and infectious diseases.