胆汁酸在脂肪肝出血综合征蛋鸡肝脏脂质代谢中的作用研究

尽管蛋鸡脂肪肝出血综合征（FLHS）发病机制不清楚，但肝脏脂质代谢紊乱导致脂质过量沉积被认为是其发生最直接的原因。胆汁酸（BAs）已被证明在肝脏脂质代谢中发挥重要作用。项目组发现，BAs及其通路因子表达下降与FLHS蛋鸡肝脏脂肪变性密切相关，提示BAs代谢改变可能是导致FLHS蛋鸡肝脏脂质代谢紊乱的主要原因，但其确切作用及机制不明。项目拟应用qPCR等方法，检测健康和FLHS蛋鸡肝脏脂肪变性、脂质代谢和BAs通路关键因子的变化，分析BAs通路变化与FLHS蛋鸡肝脏脂质代谢改变的相关性；通过体外诱导蛋鸡肝细胞脂肪变性模型，检测BAs对肝细胞脂肪变性和脂质代谢相关因子的影响；通过BAs饲喂试验，检测BAs对肝脏脂质代谢和BAs通路相关因子变化的影响；最后结合肝脏脂质代谢组学解析结果，从整体水平阐明BAs对FLHS蛋鸡肝脏脂质代谢的调控作用及机制，为揭示蛋鸡FLHS发病机制和防治提供理论依据。

Excessive lipid deposition induced by dysregulation of hepatic lipid metabolism was thought to be the primary cause of fatty liver hemorrhagic syndrome (FLHS) in laying hens, although the pathogenesis of which was still unknown. Bile acids (BAs) has been proven to taken an important role in hepatic lipid metabolism. Our previous studies found the decline in the expression levels of BAs and related factors in BAs signal pathways was closely related to hepatic steatosis in haying hens with FLHS, indicating the changes of BAs metabolism may be the crucial cause of hepatic lipid metabolism dysregulation in FLHS hens. In the present study, firstly, the relevance of BAs signal pathways and hepatic lipid metabolism of FLHS laying hens will be analyzed by the comparison of hepatic steatosis, lipid metabolism and expression levels of key factors in BAs pathways between healthy and FLHS laying hens. Secondly, the effects of BAs on liver cellular steatosis and lipid metabolism will be detected in laying hen fatty degenerative liver cells model. Thirdly, the effects of BAs on hepatic lipid metabolism and BAs signal pathways will be measured through BAs feeding FLHS layer experiment. Finally, the regulation and its mechanism of BAs on hepatic lipid metabolism of FLHS laying hens will be elucidated at the integral level through combining the above study and the results of hepatic lipid metabonomics analysis, which will provide theoretical basis for revealing the pathogenesis of FLHS and further the prevention and treatment of FLHS.