Citrin缺陷导致的新生儿肝内胆汁淤积症发病机制和治疗策略：聚焦胆小管膜载体蛋白  

Pathophysiologic and therapeutic insights into neonatal intrahepatic cholestasis caused by Citrin deficiency： focusing on the canalicular transporters

作　　者：宋元宗[1] Song Yuanzong(Department of Pediatrics,the First Affiliated Hospital of Jinan University,Guangzhou 510630,China)

机构地区：[1]暨南大学附属第一医院儿科,广州510630

出　　处：《中华实用儿科临床杂志》2018年第19期1447-1450,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金（81070279,81270957,81570793）

摘　　要：Citrin缺陷导致的新生儿肝内胆汁淤积症（neonatal intrahepatic cholestasis caused by Citrin deficiency，NICCD）发病的关键病理生理改变是肝细胞胞质NADH/NAD＋比值上升。该比值上升一方面造成NICCD患儿肝细胞能量缺乏，影响胆小管膜上BSEP、MDR3、FIC1、Sterolin 1/2和MRP2等能量依赖性载体蛋白的转运功能而造成胆汁淤积，另一方面抑制半乳糖代谢，形成继发性半乳糖血症，损伤肝细胞及眼部晶体等肝外组织。无乳糖并强化中链三酰甘油的特殊配方奶粉，可迅速纠正肝细胞能量缺乏和继发性半乳糖血症，从而有效改善NICCD患儿病情。The elevated NADH/NAD＋ ratio in the plasma of the hepatocyte is a key pathophysiologic alteration for the development of neonatal intrahepatic cholestasis caused by Citrin deficiency （NICCD）. The elevated ratio results in energy shortage in hepatocytes and impairs the function of the ATP-dependent canalicular transporters, including BSEP, MDR3, FIC1, Sterolin 1/2 and MRP2, leading to intrahepatic cholestasis in NICCD patients.On the other hand, the increased NADH/NAD＋ ratio inhibits galactose metabolism and thus gives rise to secondary galactosemia, damaging the hepatocyte as well as extrahepatic organs including the lens of the eyes.The lactose-free and medium-chain triglyceride-enriched formulas can rapidly correct the energy shortage of the hepatocyte and alleviate secondary galactosemia, hence improving the clinical presentations effectively in NICCD patients.

关 键 词：CITRIN缺陷病 胆汁淤积症 胆小管 转运蛋白 

分 类 号：R722.1[医药卫生—儿科]