喻鹏久,梁峰华,银雪艳,谢慧
YU Pengjiu,LIANG Fenghua,YIN Xueyan,XIE Hui

• 1:广州医科大学附属第一医院药学部

摘要(Abstract)：

目的研究奥氮平对人肝细胞株Hep G2中黏附分子ICAM-1表达的影响,探讨奥氮平诱导代谢综合征的作用机制。方法使用奥氮平刺激hepg2细胞,实时荧光定量PCR(real-time PCR)法检测奥氮平对细胞中ICAM-1 mRNA表达的影响;Western blot法检测奥氮平对细胞中ERK1/2信号通路的影响。结果奥氮平(10μmol/L)在给药4、8、12、24 h后均可诱导ICAM-1 mRNA的表达,同时在3~30μmol/L浓度范围内具有剂量依赖性,3、10和30μmol/L剂量诱导的ICAM-1 mRNA表达量分别为对照组细胞的1.27±0.27、2.15±0.54和2.34±0.48倍;奥氮平在给药24 h内可持续诱导Hepg2细胞中ERK1/2蛋白的磷酸化,使用ERK1/2通路抑制剂U0126可明显抑制奥氮平诱导的ICAM-1的mRNA表达(P<0.01)。结论奥氮平可通过ERK1/2通路诱导人肝细胞株中ICAM-1 mRNA的表达,这可能是该药诱导代谢综合征的作用机制。
OBJECTIVE To investigate the effect of olanzapine on ICAM-1 mRNA expression in hepatocyte,so as to explore the mechanism of metabolic syndrome induced by olanzapine. METHODS The effect of olanzapine on ICAM-1 mRNA expression was examined by real-time PCR. The effect of olanzapine on ERK1 /2 signalling pathway was examined by Western Bolt. RESULTS Olanzapine significantly induced the ICAM-1 mRNA expression in a dose-dependent(0- 30 μmol / L) and time-dependent(0- 24 h)manner. Olanzapine also markedly induced the phosphorylation of ERK1 /2 protein. The ICAM-1 mRNA expression induced by olanzapine was significantly inhibited by U0126. CONCLUSION Olanzapine induces the hepatocellular ICAM-1 mRNA expression via activation of ERK1 /2 pathway.

关键词(KeyWords)： 奥氮平;人肝细胞株;ICAM-1;ERK1/2
olanzapine;hepatocyte;ICAM-1;ERK1 /2

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 喻鹏久,梁峰华,银雪艳,谢慧
YU Pengjiu,LIANG Fenghua,YIN Xueyan,XIE Hui

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