血清胆汁酸谱检测及其在妊娠肝内胆汁淤积症中的作用

妊娠肝内胆汁淤积症（ICP）是一种对母婴，特别是围生儿造成严重危害的妊娠并发症。其发病机制不明，也无特异的诊断与分度指标。研究显示，肝胆疾病时胆汁酸代谢异常，且不同疾病有其特征的胆汁酸谱。由于某些胆汁酸在体内含量极低，且胆汁酸本身又无电化学信号，但在氧化型辅酶I (NAD+)共存下，能被3α-羟类固醇脱氢酶(3α-HSD )催化脱氢生成3-酮类固醇，NAD+还原为还原型辅酶I (NADH)。在工作电极上施加恒电位使NADH被氧化为NAD+，产生电化学响应，从而可通过电化学法实现血清胆汁酸谱的高灵敏度检测。PDMS芯片具有成本低、快速分离等特点。本项目将高效分离的PDMS芯片和高灵敏度的电化学检测偶联建立胆汁酸谱检测新方法，用于ICP患者血清胆汁酸谱分析，以期建立ICP特异诊断和分度模式，有望筛选出特异的ICP生物标志物，并为理解ICP的发病机制提供依据。

Intrahepatic cholestasis of pregnancy (ICP) is a complication of pregnancy that would cause serious damages to mother and infant, especially to perinatal infant. Its pathogenesis has not been clearly understood, neither is the specific diagnostic indicator and grading criteria. Researches showed that abnormal bile acid metabolism occured in hepatobiliary diseases. Furthermore, different diseases had their characterized bile acids profiling. Because of some bile acids have very low concentration in vivo, and bile acids themselves have no electrochemical signals. But with the coexisting of nicotinamide adenine dinucleotide (NAD+), bile acids are converted to 3-ketosteroids under the catalysis of 3α-hydroxysteriod dehydrogenase (3α-HSD) with concomitant reduction of NAD+ to reduced nicotinamide adenine dinucleotide (NADH). With an appropriate voltage applied on the working electrode, NADH is oxidized to form NAD+, which results in electrochemical signal and could analyze the serum bile acids profiling with high sensitivity by the electrochemical detection. Polydimethylsiloxane (PDMS) chips have the characteristics of low cost and fast separation. This project plans to interconnect the high efficiency of PDMS chip in separation and high sensitivity of electrochemical method in detection to develop a new method for the analysis of bile acids profiling. And next, the method could be applied to the detection of serum bile acids profiling in ICP patients. The aim is to develop the specific diagnosis and grading criteria of ICP and select the specific biomarkers for ICP, which could also provide a prospective basis to understand the pathogenesis of ICP.