妊娠肝内胆汁淤积症患者血清甘胆酸水平变化与胎盘细胞凋亡调节基因表达的关系

目的　探讨妊娠肝内胆汁淤积症 (ICP)患者血清甘胆酸水平变化与胎盘细胞凋亡的关系 ,进一步分析ICP患者胎盘功能减退的可能机制。方法　应用放射免疫方法 ,测定 30例ICP患者(ICP组 )及 2 7例正常孕妇 (对照组 )分娩前血清甘胆酸水平 ,应用免疫组化方法测定两组孕妇胎盘细胞凋亡调节基因bax和bcl 2的表达。结果　 (1)ICP组甘胆酸水平为 (5 1 8± 5 9) μmol/L ,对照组为(9 4± 5 6 ) μmol/L ,两组比较 ,差异有显著性 (P <0 0 5 )。 (2 )ICP组胎盘合体滋养细胞bax阴性 2例 ,弱阳性 9例 ,中等阳性 11例 ,强阳性 8例 ;bcl 2弱阳性 12例 ,中等阳性 12例 ,强阳性 6例。对照组bax阴性 9例 ,弱阳性 13例 ,中等阳性 4例 ,强阳性 1例 ;bcl 2弱阳性 3例 ,中等阳性 4例 ,强阳性 2 0例。两组比较 ,ICP组bax表达阳性率显著高于对照组 (P <0 0 0 0 5 ) ,而bcl 2的表达阳性率又显著低于对照组 (P <0 0 0 0 5 )。 (3)孕妇血甘胆酸水平与胎盘bax表达阳性率呈线性正相关 (P <0 0 0 5 ) ,与胎盘bcl 2表达呈线性负相关 (P <0 0 0 5 )。结论　ICP患者血中高水平的甘胆酸使胎盘合体滋养细胞bax基因过度表达 ,这可能是ICP患者胎盘功能减退的机制之一。

Study on relationship between serum cholylglycine and placental apoptosis in patients with intrahepatic cholestasis of pregnancy

OBJECTIVE: To explore the possible mechanism of placental dysfunction in patients with intrahepatic cholestasis of pregnancy (ICP). METHODS: Serum level of cholylglycine (CG) in 30 cases with ICP (ICP group) and 27 normal pregnant women (control group) was examined by radio-immunoassay before delivery. bax and bcl-2 level in placenta was detected by immunohistochemistry method. RESULTS: (1) Serum CG level in ICP group was (51.8 +/- 5.9) micro mol/L, and in control group it was (9.4 +/- 5.6) micro mol/L. The difference between the two groups was significant (P < 0.05). (2) bax expression level in syncytiotrophoblast of ICP group was: 2(-), 9(+), 11 (++), 8(+++), and bcl-2 expression level was: 12(+), 12(++), 6(+++); bax expression level in control group was: 9 (-), 13(+), 4(++), 1(+++) and bcl-2 expression level was: 3(+), 4(++), 20(+++). bax expression level in syncytiotrophoblast of ICP group was higher than that of the control (P < 0.0005), and bcl-2 expression level was lower than in the control (P < 0.0005), both significantly. A significant positive correlation between CG level and bax expression level and a negative correlation between CG and bcl-2 were found in ICP group (P < 0.005, P < 0.005). CONCLUSION: One of the possible mechanisms involved in placental dysfunction of ICP is overexpression of bax in syncytiotrophoblast caused by high concentrations of bile acid, leading to increased apoptosis.