胆道闭锁实验动物模型的比较

Comparison of experimental animal models of biliary atresia

胆道闭锁(biliary atresia,BA)是新生儿时期导致肝移植的重要病因之一,近年来随着诊断技术的提高,本病的发病率也在不断上升,但本病的具体病因及发病机制尚不明确,动物模型的出现是探索本病的重要途径。但国内对本病的认识及相关动物模型的研究还相对滞后,目前BA模型主要分为药物毒物诱导型、胆道机械结扎型、轮状病毒诱导型3大类,其中药物毒物诱导的BA模型对胆管具有选择性,目前还存在诸多尚未解决的问题;胆道结扎的方法虽然造成胆管闭锁,但和真实世界的BA存在发病年龄等不相符的情况;而轮状病毒诱导胆管闭锁模型目前被广泛接受,也是当前主要的研究模型,但是在肝纤维化形成之前,模型动物均已死亡,也不能充分反映BA的疾病进展过程;而采用轮状病毒基因重组方法建立的动物模型有存活时间相对较长,并且可以实现肝纤维化的优点,更接近实际的病理发展过程,是具有前景的模型。总的来讲,BA的研究尚缺乏完全符合临床实际,充分反映临床疾病发展的理想动物模型。

Biliary atresia(BA)is an important indication for liver transplantation during the neonatal period.With the improvement in diagnostic techniques in recent years,the diagnosis rate for BA is increasing continuously.However,the specific etiology and pathogenesis of BA remains unclear.Related knowledge and research models for BA are still relatively limited in China.At present,the BA models are divided mainly into three categories:drug or poisoninduced,mechanical biliary tract ligation and rotavirus-induced.Among them,the drug-poison-induced BA model is selective to the bile duct,and there are still many unsolved problems.Although the method of biliary ligation causes bile duct atresia,it is inconsistent with the onset age of BA in the real world.The rotavirus-induced bile duct atresia model is widely accepted and is the main research model at present;however,all of the animals die before the formation of liver fibrosis,and this model does not fully reflect the disease progression process of BA.The rotavirus gene recombination method may result in liver fibrosis and is a promising model because the survival time of the animals is relatively long,and the model more closely relates to the actual pathological process.In general,BA still lacks an ideal animal model that fully conforms to clinical practice and reflects the development of clinical disease.