妊娠期肝内胆汁淤积症孕妇胎盘组织HDAC3的表达及意义研究

Expression of histone deacetylase 3 in placenta with intrahepatic cholestasis of pregnancy and its significance

摘要:

目的：探讨组蛋白去乙酰化酶3（histone deacetylase 3，HDAC3）在妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy，ICP）孕妇胎盘组织中的表达及意义。方法：2012年3月至2013年5月在重庆医科大学附属第一医院选择ICP孕妇41例为研究对象，包括ICP轻度组（19例）、ICP重度组（22例），以同期行择期剖宫产术的20例正常孕妇为对照组。免疫组化法检测胎盘组织中HDAC3的定位及表达，蛋白印迹（Western blot）技术检测胎盘组织中HDAC3蛋白的表达水平，实时荧光定量PCR（real-time PCR）技术检测胎盘组织中HDAC3 mRNA的表达水平。结果：（1）ICP重度组孕妇血清中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、总胆汁酸（total bile acid，TBA）及谷草转氨酶（glutamic-oxaloacetic transaminase，AST）、谷丙转氨酶（glutamic-pyruvic transaminase，ALT）水平明显高于轻度组和正常对照组，差异有统计学意义（P<0.05）。（2）ICP重度组和轻度组胎盘组织中HDAC3蛋白和mRNA的表达水平均低于对照组，分别比较差异均有统计学意义（P＜0.05）。（3）胎盘组织中HDAC3蛋白表达水平与血清中TNF-α、TBA及ALT、AST水平呈负相关。结论：HDAC3表达下调可能与ICP发病及肝功能损害有关。

Abstract:

Objective：To evaluate the expression and location of the histone deacetylase3（HDAC3） in human placenta with intrahep－atic cholestasis of pregnancy（ICP） and its significance. Methods：Fourty-one women with ICP who delivered from March 2012 to May 2013 in the First Affiliated Hospital of Chongqing Medical University were chosen as the study objects.They were classified into mild group（n=19），severe group（n=22）. Twenty healthy pregnant women who delivered in the same period were chosen as the control group（n=20）. Immunohistochemical was employed to detect the expression and localization of HDAC3 protein in placenta tissue. Western blot analysis was used to quantify HDAC3 protein expression level. Real-time PCR was used to quantify HDAC3 mRNA expression level. Results：（1）The serum levels of tumor necrosis factor-α（TNF-α），total bile acid（TBA），glutamic-oxaloacetic transaminase（ALT） and glutamic-pyruvic transaminase（AST） were significantly higher in severe groups than in mild ICP group and control group（P<0.05）.（2）The HDAC3 protein and mRNA levels in placenta were significantly lower in severe and mild groups than in control group（P<0.05）． （3）The quantitative expression of HDAC3 protein in placenta was negatively correlated with serum TNF-α，TBA，ALT and AST levels. Conclusion：The low expression of HDAC3 may be associated with the pathogenesis of ICP and liver function damage.