Yang Xiu-Fang, Liu Guo-Sheng, Chen Yu-Lan, Chen Jian, Lin Qiang, Huang Hui-Juan, Zheng Kai-Jun
Department of Neonatology, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan, Guangdong 528403, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2019 Feb;21(2):125-130. doi: 10.7499/j.issn.1008-8830.2019.02.004.
To study the association between the expression of the MDR3 gene and the pathogenesis of parenteral nutrition-associated cholestasis (PNAC) in preterm infants.
Among the preterm infants who were admitted to the hospital from June 2011 to November 2017 and received parenteral nutrition for more than 14 days, 80 who did not develop PNAC were enrolled as non-PNAC group, and 76 who developed PNAC were enrolled as PNAC group. On days 1, 14, 30, 60 and 90 after birth, serum hepatobiliary biochemical parameters [alanine aminotransferase (ALT), total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA) and gamma-glutamyl transpeptidase (γ-GT)], fibrosis indices [hyaluronic acid, laminin, procollagen III N-terminal peptide and type IV collagen] and clinical manifestations were observed. Real-time quantitative PCR was used to measure the mRNA expression of MDR3 in both groups, and the correlation between the mRNA expression of MDR3 and serum hepatobiliary biochemical parameters was analyzed.
In the PNAC group, serum levels of hepatobiliary biochemical parameters and fibrosis indices increased on day 14 after birth and reached the peak on day 30 after birth, followed by a reduction on day 60 after birth. On days 14, 30, 60 and 90 after birth, the PNAC group had significantly higher serum levels of hepatobiliary biochemical parameters and fibrosis indices than the non-PNAC group (P<0.05). The PNAC group had higher relative mRNA expression of MDR3 in peripheral blood cells than the non-PNAC group (P<0.05). In the PNAC group, the relative mRNA expression of MDR3 in peripheral blood cells was negatively correlated with serum levels of hepatobiliary biochemical parameters (ALT, TBil, DBil, TBA and γ-GT) (P<0.001).
High mRNA expression of MDR3 in preterm infants may be associated with the development of PNAC, and further studies are needed to identify the mechanism.
研究多药耐药蛋白3（MDR3）基因表达与早产儿肠外营养相关性胆汁淤积（PNAC）发病机制之间的关联。
选取2011年6月至2017年11月期间入院且接受肠外营养超过14天的早产儿，将其中未发生PNAC的80例纳入非PNAC组，发生PNAC的76例纳入PNAC组。在出生后第1、14、30、60和90天，观察血清肝胆生化指标[丙氨酸氨基转移酶（ALT）、总胆红素（TBil）、直接胆红素（DBil）、总胆汁酸（TBA）和γ-谷氨酰转肽酶（γ-GT）]、纤维化指标[透明质酸、层粘连蛋白、Ⅲ型前胶原N端肽和Ⅳ型胶原]及临床表现。采用实时定量PCR检测两组中MDR3的mRNA表达，并分析MDR3的mRNA表达与血清肝胆生化指标之间的相关性。
PNAC组出生后第14天血清肝胆生化指标及纤维化指标水平升高，出生后第30天达到峰值，随后在出生后第60天下降。在出生后第14、30、60和90天，PNAC组血清肝胆生化指标及纤维化指标水平显著高于非PNAC组（P<0.05）。PNAC组外周血细胞中MDR3的相对mRNA表达高于非PNAC组（P<0.05）。在PNAC组中，外周血细胞中MDR3的相对mRNA表达与血清肝胆生化指标（ALT、TBil、DBil、TBA和γ-GT）水平呈负相关（P<0.001）。
早产儿MDR3的高mRNA表达可能与PNAC的发生有关，需要进一步研究以明确其机制。
