胃肠外营养相关性胆汁淤积症早产儿血MDR3基因mRNA表达

mRNA expression of MDR3 gene in the blood of preterm infants with parenteral nutrition-associated cholestasis

目的研究MDR3基因表达与早产儿胃肠外营养相关性胆汁淤积症(PNAC)发病的相关性。方法将2011年6月至2017年11月收治的行胃肠外营养超过14 d且未合并PNAC的早产儿80例为非PNAC组,患有PNAC的早产儿76例为PNAC组,所有研究对象均分别于生后1、14、30、60、90 d动态观察血清肝胆生化(丙氨酸氨基转移酶、总胆红素、直接胆红素、总胆汁酸和γ-谷氨酰转肽酶)及纤维化指标(透明质酸、层黏连蛋白、Ⅲ型前胶原N端肽、Ⅳ型胶原)变化,以及临床表现;采用实时荧光定量PCR法检测两组MDR3 mRNA水平的相对表达量;分析MDR3 mRNA表达水平与血清肝胆生化指标的相关性。结果 PNAC组早产儿血清肝胆生化及纤维化指标水平在生后14 d上升,至生后30 d达最高峰,生后60 d下降,且PNAC组生后第14、30、60、90天的血清肝胆生化及纤维化指标均高于非PNAC组(P<0.05)。PNAC组早产儿外周血细胞MDR3 mRNA的相对表达水平高于非PNAC组(P<0.05)。PNAC组患儿外周血细胞MDR3 mRNA的相对表达量与血清肝胆生化指标水平(丙氨酸氨基转移酶、总胆红素、直接胆红素、总胆汁酸和γ-谷氨酰转肽酶)均呈负相关(P<0.001)。结论 MDR3 mRNA高表达可能与早产儿PNAC发病有关,但具体机制仍需进一步研究探讨。

Objective To study the association between the expression of the MDR3 gene and the pathogenesis of parenteral nutrition-associated cholestasis(PNAC) in preterm infants. Methods 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. Results 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 m RNA 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). Conclusions High m RNA expression of MDR3 in preterm infants may be associated with the development of PNAC, and further studies are needed to identify the mechanism.