摘要
目的探讨防治内毒素休克的新方法，研究脂多糖（ＬＰＳ）诱导肿瘤坏死因子α（ＴＮＦα）表达的分子机制。方法用蛋白激酶活性测定检测ＬＰＳ刺激引起的激酶活性变化；共聚焦激光扫描技术显示ｐ３８激活移位；用反转录聚合酶链反应和报告基因系统研究ＴＮＦα基因转录的分子机制。结果发现ＬＰＳ刺激ＲＡＷ细胞引起ｐ３８激活并由胞浆移位至胞核。ＬＰＳ刺激引起ＴＮＦαｍＲＮＡ表达增加，而且由ＬＰＳ引起的ＴＮＦα的转录活性可被ｐ３８特异性抑制剂所抑制。结论激活的ｐ３８通过磷酸化转录因子增加ＴＮＦα基因转录活性，这是中毒性休克时ＴＮＦα生成增加的一个重要机制。ｐ３８是ＬＰＳ诱导ＴＮＦα基因表达的重要调节物质。
Objective
To study the molecular mechanisms of TNF expression induced by LPS for the exploring of
novel methods to prevent and treat clinical patients of endotoxic shock. Methods Protein kinase
assay was used to detect the kinase activity stimulated by LPS; Confocal laser scan technique
was used to show the translocation of p38 on the activation; RTPCR and reporter gene system
were used to study the molecular mechanism of TNF gene transcription. Results In RAW cells,
p38 was activated on the stimulation of LPS, and activated p38 moved into nucleus from
cytosol. TNF mRNA increased on the stimulation of LPS and the increased promoter
transactivity induced by LPS could be inhibited significantly by specific inhibitor for p38.
Conclusion p38 MAPK was activated on the stimulation of LPS, which brought about its
translocation to the nucleus to act on transcription factors to regulate cellular processes. p38
MAPK is an important regulator of TNF gene expression induced by LPS.
出处
《中华医学杂志》
CAS
CSCD
北大核心
1999年第5期360-364,共5页
National Medical Journal of China
基金
国家自然科学基金
军队杰出人才基金
军队留学回国人员启动基金
广东省自然科学基金
