Tivers Michael S, Handel Ian, Gow Adam G, Lipscomb Victoria 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. 2015 Feb 6;10(2):e0117557. doi: 10.1371/journal.pone.0117557. eCollection 2015.
Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital portosystemic shunt is one of the most common congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a congenital portosystemic shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of congenital portosystemic shunts in dogs. One hundred and forty dogs with a congenital portosystemic shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical congenital portosystemic shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of congenital portosystemic shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder.
肝脏疾病是发病和死亡的主要原因。肝病患者最严重的并发症之一是出现神经功能紊乱，即肝性脑病。肝性脑病的发病机制尚未完全明确，这导致了多种实验模型的开发。先天性门体分流是宠物犬中最常见的先天性疾病之一。我们最近的研究表明，犬肝性脑病的病理生理学与人类肝性脑病非常相似，这为将患有先天性门体分流的犬作为人类肝性脑病的自然发生模型提供了有力支持。具体而言，我们已经证明氨和炎症在患有先天性门体分流的犬肝性脑病发展中起重要作用。尽管炎症在犬肝性脑病的发生中显然很重要，但尚不清楚肝病成功治疗后炎症是否会消退。我们假设，通过中性粒细胞、淋巴细胞和单核细胞浓度以及C反应蛋白浓度来衡量的炎症的血液学和生化证据，在犬先天性门体分流成功治疗后会降低。140只患有先天性门体分流的犬被纳入该研究。我们发现，在初次诊断时患有肝性脑病的犬中，单核细胞浓度高于参考范围的犬的比例显著更高。重要的是，先天性门体分流手术减流后，中性粒细胞和单核细胞浓度显著降低。我们还发现，先天性门体分流手术减流后，C反应蛋白浓度显著降低。我们的研究表明，潜在肝脏疾病成功治疗后，炎症的血液学和生化指标会降低。
