过氧化物酶体增殖物激活受体-α对妊娠期肝内胆汁淤积症代谢的影响及调控机制

Effect of peroxisome proliferators-activated receptors-α on metabolism of intrahepatic cholestasis disease patients and regulation mechanism

目的探讨过氧化物酶体增殖物激活受体-α(PPAR-α)信号通路对妊娠期肝内胆汁淤积症(ICP)代谢的影响,初步揭示ICP肝功能异常的发病可能机制,为其防治提供理论基础。方法收集2013年1月-2014年1月于该院就诊人群的正常妊娠胎盘组织和ICP妊娠胎盘组织各30例;体外分离和培养胎盘组织,双抗体夹心酶联免疫吸附试验(ELISA)分别测定胎盘组织培养上清液和组织中的PPAR-α、雌激素受体α(ERα)及雌激素受体β(ERβ)的表达水平;采用PPAR-α激活物培养ICP患者组织,对ICP患者胎盘组织活性进行检测,采用反转录聚合酶链反应(RT-PCR)检测胎盘组织中PPAR-α、ERα及ERβ的m RNA表达,蛋白质免疫印迹法(Western blot)检测胎盘组织中PPAR-α、ERα及ERβ的蛋白表达。结果 ICP患者胎盘组织培养液和胎盘组织中PPAR-α的表达较对照组均明显下调,而ERα和ERβ的表达较对照组均明显上调;使用PPAR-α激活剂处理的ICP患者胎盘组织活性明显提高;使用PPAR-α激活剂处理的胎盘组织中ERα和ERβ的m RNA水平和蛋白水平表达明显下调。结论 PPAR-α可能通过上调ERα和ERβ的表达促进了ICP的发生,可作为临床上防治ICP的分子靶点。

Objective To explore the effect of peroxisome proliferators-activated receptors-α（ PPAR-α） signaling pathway on metabolism of intrahepatic cholestasis disease patients,reveal the pathogenesis of abnormal liver function of ICP patients,provide theoretical basis for prevention and treatment. Methods Placental tissue samples of 30 normal pregnant women and 30 ICP patients were collected from January 2013 to January 2014 in the hospital,then the samples were isolated and cultured in vitro,the expression levels of PPAR-α,estrogen receptor α（ ER α）,and estrogen receptor β（ ER β） in placental tissue culture supernatant and organization were detected through double antibody sandwich enzyme-linked immunosorbent assay（ ELISA）. PPAR-α activator was used to treat ICP patients,placental tissue activity was detected,RT-PCR was used to detect expression levels of PPAR-α m RNA,ER α m RNA,and ER β m RNA,Western blot was used to detect the expression levels of PPAR-α protein,ER α protein,and ER β protein. Results The expression levels of PPAR-αin placental tissue culture supernatant and organization of ICP patients were significantly lower than those in control group,while the expression levels of ER α and ER β were significantly higher than those in control group; placental tissue activity increased significantly after treated by PPAR-α activator in ICP patients; the expression levels of ER α and ER β m RNA and proteins were significantly downregulated after treated by PPAR-α activator. Conclusion PPAR-α may promote the occurrence of ICP through upregulating the expression levels of ERαand ER β,which can be used as a molecular target for prevention and treatment of ICP.