Tivers Mickey S, Handel Ian, Gow Adam G, Lipscomb Vicky J, Jalan Rajiv, Mellanby Richard J
Department of Veterinary Clinical Sciences, Royal Veterinary College, Hatfield, Hertfordshire, United Kingdom.
Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Roslin, Midlothian, United Kingdom.
PLoS One. 2014 Jan 2;9(1):e82303. doi: 10.1371/journal.pone.0082303. eCollection 2014.
Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced.
肝性脑病(HE)是肝病患者发病和死亡的重要原因。尽管氨和炎性细胞因子被认为是关键介质,但其发病机制尚未完全明确。为了进一步从机制上理解HE的发病机制,人们建立了大量动物模型,这些模型通常涉及在肝门静脉和尾腔静脉之间进行手术吻合。犬类最常见的先天性异常之一是先天性门体分流(CPSS),它与这些HE的手术实验模型极为相似。患有CPSS的犬类通常具有与患有HE的人类相似的临床症状。我们的假设是,患有CPSS的犬类HE发病机制与人类相似。本研究的目的是测量一系列与人类HE发展相关的临床、血液学和生化参数,这些参数来自患有CPSS且已知HE分级的犬类。120只患有CPSS的犬类被纳入研究,对临床、血液学和生化变量进行的多元回归分析显示,血浆氨浓度和全身炎症反应综合征评分可预测HE的存在。我们的研究结果进一步支持了犬类和人类HE发病机制有许多相似之处的观点,并表明患有CPSS的犬类可能是人类HE的一个有参考价值的自发模型。对患有CPSS的犬类进行进一步研究,可能使HE研究无需创建手术模型,从而减少动物实验中所用大型动物的数量。