内毒素诱导大鼠肝细胞白蛋白表达下降的分子机制

Potential mechanism underlying down-regulation of albumin expression induced by lipopoly-saccharide in rat hepatocytes

目的 探讨内毒素诱导肝细胞白蛋白表达下降的分子机制。方法 1μg/ml内毒素刺激肝细胞后 ,分别在 0 ,2 ,8,12和 2 4h时留取肝细胞及上清检测白蛋白mRNA及其蛋白水平的变化。细胞内信号蛋白p38激酶和ERK激酶的特异性阻断剂SB2 0 35 80和PD980 5 9预处理肝细胞后检测上清中白蛋白的浓度。结果 内毒素刺激后 2 4h白蛋白mRNA下降约为 30 % ,与此同时白蛋白浓度下降约 5 0 %。SB2 0 35 80和PD980 5 9可以在体外抑制内毒素诱导肝细胞白蛋白表达的下降。结论 内毒素在转录水平抑制肝细胞白蛋白mRNA的表达来抑制白蛋白的合成。这一过程与细胞内信号传导通路p38和ERK激酶密切相关 ,进一步阐明了感染时低白蛋白血症的分子机制。

Objective To investigate the potential molecular mechanism underlying down regulation of albumin expression induced by lipopolysaccharide (LPS) in rat hepatocytes Methods The albumin mRNA expression and albumin protein levels in the supernatant were observed at 0,2,8,12 and 24 hours after 1μg/ml LPS treatment The albumin mRNA expression was determined by RT PCR,and albumin protein levels were assayed with EIA in the supernatant of hepatocytes pretreated with specific inhibitors of extracellular signal regulated kinase (PD98059) and p38 kinase (SB203580) Results The albumin mRNA expression was reduced to 70% of baseline value,meanwhile,the albumin protein concentration in the supernatant was reduced by 50% compared with the controls after 24 hours of LPS treatment Pretreatment with PD98059 and SB203580 did significantly inhibit the reduction of albumin by LPS at the given dose Conclusion The results indicate that LPS can induce the reduction of albumin synthesis by down regulation of albumin mRNA expression at transcription level,and the process may be related to the signal transducation of extracellular signal regulated kinase and p38 kinase