Vince Andrew R, Hayes M Anthony, Jefferson Barbara J, Stalker Margaret J
Animal Health Laboratory, Laboratory Services Division (Vince, Stalker), University of Guelph, Guelph, Ontario, CanadaDepartment of Pathobiology, Ontario Veterinary College (Hayes, Jefferson), University of Guelph, Guelph, Ontario, Canada
Animal Health Laboratory, Laboratory Services Division (Vince, Stalker), University of Guelph, Guelph, Ontario, CanadaDepartment of Pathobiology, Ontario Veterinary College (Hayes, Jefferson), University of Guelph, Guelph, Ontario, Canada.
J Vet Diagn Invest. 2016 Sep;28(5):498-505. doi: 10.1177/1040638716658499. Epub 2016 Jul 16.
We evaluated the extent of hepatic fibrosis in chronic liver disease of dogs using a modification of Ishak's staging criteria for human chronic liver disease, and examined the association of stage of fibrosis with immunophenotypic markers of transdifferentiation of hepatic sinusoidal endothelial cells and hepatic stellate cells. Formalin-fixed, paraffin-embedded, hematoxylin and eosin-stained liver biopsy specimens from 45 case dogs with chronic liver disease and 55 healthy control dogs were scored for the presence and extent of fibrosis. This stage score for fibrosis strongly correlated with upregulated von Willebrand factor (vWF) expression in lobular sinusoidal endothelial cells (Spearman correlation coefficient [SCC] = 0.57, p < 0.05). Immunoreactivity for vWF factor was identified in 68.9% of case biopsies, varying in distribution from periportal to diffuse, whereas vWF immunoreactivity was identified in only 14.5% of control specimens, and was restricted to the immediate periportal sinusoids. The majority of both case and control biopsies exhibited similar prominent lobular perisinusoidal expression of alpha-smooth muscle actin (α-SMA). A minority of specimens (17.8% of case biopsies, 1.8% of control biopsies) exhibited low perisinoidal α-SMA expression, and there was a weak negative correlation between α-SMA expression and stage of fibrosis (SCC = -0.29, p = 0.0037). These results document a method for staging the severity of fibrosis in canine liver biopsies, and show a strong association between fibrosis and increased expression of vWF in hepatic sinusoidal endothelial cells.
我们采用对人类慢性肝病的伊沙克分期标准进行修改的方法，评估了犬类慢性肝病中肝纤维化的程度，并研究了纤维化阶段与肝窦内皮细胞和肝星状细胞转分化免疫表型标志物之间的关联。对45只患有慢性肝病的病例犬和55只健康对照犬的福尔马林固定、石蜡包埋、苏木精和伊红染色的肝活检标本进行纤维化存在情况和程度评分。这种纤维化阶段评分与小叶窦内皮细胞中血管性血友病因子（vWF）表达上调密切相关（斯皮尔曼相关系数[SCC]=0.57，p<0.05）。在68.9%的病例活检中发现了vWF因子的免疫反应性，其分布从门静脉周围到弥漫性不等，而在仅14.5%的对照标本中发现了vWF免疫反应性，且仅限于紧邻门静脉周围的窦状隙。病例和对照活检标本中的大多数都表现出相似的小叶窦周α-平滑肌肌动蛋白（α-SMA）突出表达。少数标本（17.8%的病例活检，1.8%的对照活检）表现出低窦周α-SMA表达，且α-SMA表达与纤维化阶段之间存在弱负相关（SCC=-0.29，p=0.0037）。这些结果记录了一种对犬肝活检纤维化严重程度进行分期的方法，并表明纤维化与肝窦内皮细胞中vWF表达增加之间存在密切关联。
