Tinmouth Jill, Lee Mary, Wanless Ian R, Tsui Florence W L, Inman Robert, Heathcote E Jenny
Department of Medicine, University Health Network, Toronto, Ontario, Canada.
Liver. 2002 Jun;22(3):228-34. doi: 10.1046/j.0106-9543.2002.01595.x.
BACKGROUND/AIMS: Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by inflammatory destruction of small bile ducts. Primary sclerosing cholangitis (PSC) is a different, presumed autoimmune cholestatic liver disease where the bile ducts are also destroyed. In this study, apoptosis and portal triad inflammation in liver tissue from patients with PBC is examined and compared to that from patients with PSC and patients with normal liver.
Explanted liver tissue from patients with PBC and PSC and normal liver from patients with metastases to liver were examined. The liver samples were stained for apoptosis using the terminal deoxynucleotidyl triphosphate (TdT)-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay. The biliary epithelial cells (BEC) were then scored on the basis of their TUNEL stain and the degree of periductal inflammation.
In PBC, apoptosis of BEC, as detected by the TUNEL assay, was significantly increased in the presence of inflammation. Regardless of the presence or absence of inflammation, the small bile ducts in PBC liver tissue exhibited greater evidence of apoptosis than did similar ducts from PSC or control livers.
These findings suggest that in PBC, unlike PSC, the apoptosis of BEC in PBC is secondary to the invasion of inflammatory cells.
背景/目的:原发性胆汁性肝硬化(PBC)是一种自身免疫性疾病,其特征为小胆管的炎性破坏。原发性硬化性胆管炎(PSC)是一种不同的、推测为自身免疫性胆汁淤积性肝病,胆管同样会被破坏。在本研究中,对PBC患者肝组织中的细胞凋亡和门管区炎症进行检测,并与PSC患者及肝脏正常患者的肝组织进行比较。
对PBC和PSC患者的移植肝组织以及肝转移患者的正常肝脏进行检查。使用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记(TUNEL)法对肝样本进行凋亡染色。然后根据胆管上皮细胞(BEC)的TUNEL染色及导管周围炎症程度进行评分。
在PBC中,通过TUNEL法检测发现,存在炎症时BEC的凋亡显著增加。无论有无炎症,PBC肝组织中的小胆管比PSC或对照肝脏中的类似胆管表现出更明显的凋亡迹象。
这些发现表明,与PSC不同,PBC中BEC的凋亡继发于炎性细胞的浸润。