急性缺氧对妊娠期肝内胆汁淤积症患者胎盘组织HIF-1α表达的影响及与P53表达相关性研究  

The Relationship Between P53 and Hypoxia-inducible Transcription Factor-1α in the Placenta of Patient with Intrahepatic Cholestasis of Pregnancy under Acute Hypoxic Condition

作　　者：胡雅毅[1] 王晓东[1] 刘淑芸[1] 

机构地区：[1]四川大学华西第二医院妇产科,成都610041

出　　处：《四川大学学报（医学版）》2006年第6期901-903,942,共4页Journal of Sichuan University(Medical Sciences)

基　　金：教育部博士点基金(20020610030)资助

摘　　要：目的探讨缺氧诱导因子(hypoxiainduciblefactor,HIF)在妊娠期肝内胆汁淤积症(intrahepaticcholestasisofpregnancy,ICP)患者胎盘上的表达及意义。方法体外缺氧培养ICP患者和正常晚孕妇女胎盘绒毛组织,采用免疫组织化学染色技术,观察胎盘组织HIF-1α、P53蛋白表达的变化。结果1常氧下(21%O2)ICP患者胎盘组织HIF-1α的表达和正常晚孕妇女差异无统计学意义(P>0.05),P53的表达明显高于正常晚孕组(P<0.01);22%O2低氧浓度下培养4h后ICP胎盘上HIF-1α的表达明显高于正常晚孕组(P<0.05),P53的表达显著高于正常晚孕组(P<0.001);3缺氧前后P53在ICP患者胎盘上的变化均高于正常晚孕组(P<0.01),并且,ICP胎盘上P53的变化与HIF-1α的变化呈正相关(r=0.862,P<0.01)。结论ICP胎儿缺氧时HIF-1α的应激性升高对于其适应缺氧有重要意义,它在一定程度上直接影响细胞凋亡调控基因P53的变化。失代偿的结果可能引起滋养细胞凋亡异常增加,影响ICP胎盘功能导致胎儿缺氧甚至死亡。Objective Owing to the molecu1αr mechanisms unexplored yet to fetal hypoxia signaling in the intrahepatic cholestasis of pregnancy （ICP）, and therefore we intend to investigate the significant expression of the hypoxia-inducible transcription factor-1α （HIF-1α） in p1αcenta of pregnant women with ICP during hypoxia. Methods The villous p1αcenta tissues were in vitro cultured under hypoxia condition. The immuno-histochemistry technique was applied to probe the HIF-1α and P53 expressions in p1αcentas of pregnant women and patient with ICP. Results Under the condition of normal concentration oxygen, P53 was highly expressed in the p1αcenta of pregnant women with ICP（P〈0. 01）, however the HIF-1α expression was not up to higher than in normal control. Under the condition of lower concentration oxygen （2%O2）, the HIF-1α and P53 expressions were detected from the p1αcental villous tissues cultured for 4 h of normal control and patient with ICP, and with HIF- 1α and P53 proteins increased in the p1αcenta of pregnant women with ICP （P〈0.05 and P〈0. 001 respectively）. Whatever was hypoxla condition, P53 protein got always a high expression, and had a positive corre1αtion with HIF-1α expression in ICP （P〈0. 01）. Conclusion Under hypoxic conditions, high increase of HIF-1α may influence the increase of P53 directly, which may be one of the hypoxia pathogenesis factors in ICP. The fetal hypoxia and stillbirth may be the results of unba1αnce of HIF-1α and P53 which induced apoptosis under hypoxia condition.

关 键 词：胆汁淤积症 肝内 妊娠 缺氧诱导因子-1α P53 

分 类 号：R714.25[医药卫生—妇产科学]