Ma Kuifen, Chen Yihe, Liang Xingguang, Miao Jing, Zhao Qingwei
The First Affiliated Hospital, Zhejiang University, 79# Qingchun Road, Hangzhou 310003, China.
Iran J Basic Med Sci. 2017 Nov;20(11):1207-1212. doi: 10.22038/IJBMS.2017.9482.
Arachidonic Acid/5-lipoxygenase (AA/5-LOX) pathway connects lipid metabolism and proinflammatory cytokine, which are both related to the development and progression of nonalcoholic fatty liver disease (NAFLD). Therefore, the present study was designed to investigate the role of AA/5-LOX pathway in progression of NAFLD, and the effect of zileuton, an inhibitor of 5-LOX, in this model.
Animal model for progression of NAFLD was established via feeding high saturated fat diet (HFD). Liver function, HE staining, NAFLD activity score (NAS) were used to evaluate NAFLD progression. We detected the lipid metabolism substrates: free fatty acids (FFA) and AA, products: cysteinyl-leukotrienes (CysLTs), and changes in gene and protein level of key enzyme in AA/5-LOX pathway including PLA and 5-LOX. Furthermore, we determined whether NAFLD progression pathway was delayed or reversed when zileuton (1-[1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea) was administrated.
Rat model for progression of NAFLD was well established as analyzed by liver transaminase activities, hematoxylin-eosin (HE) staining and NAS. The concentrations of substrates and products in AA/5-LOX pathway were increased with the progression of NAFLD. mRNA and protein expression of PLA and 5-LOX were all enhanced. Moreover, administration of zileuton inhibited AA/5-LOX pathway and reversed the increased transamine activities and NAS.
AA/5-LOX pathway promotes the progression of NAFLD, which can be reversed by zileuton.
花生四烯酸/5-脂氧合酶（AA/5-LOX）途径连接脂质代谢和促炎细胞因子，二者均与非酒精性脂肪性肝病（NAFLD）的发生发展相关。因此，本研究旨在探讨AA/5-LOX途径在NAFLD进展中的作用，以及5-LOX抑制剂齐留通在该模型中的作用。
通过喂食高饱和脂肪饮食（HFD）建立NAFLD进展的动物模型。采用肝功能、苏木精-伊红（HE）染色、NAFLD活动评分（NAS）评估NAFLD进展。我们检测了脂质代谢底物：游离脂肪酸（FFA）和AA，产物：半胱氨酰白三烯（CysLTs），以及AA/5-LOX途径中关键酶包括磷脂酶A（PLA）和5-LOX的基因和蛋白水平变化。此外，我们确定给予齐留通（1-[1-(1-苯并噻吩-2-基)乙基]-1-羟基脲）后NAFLD进展途径是否延迟或逆转。
通过肝转氨酶活性、苏木精-伊红（HE）染色和NAS分析，成功建立了NAFLD进展的大鼠模型。随着NAFLD的进展，AA/5-LOX途径中底物和产物的浓度增加。PLA和5-LOX的mRNA和蛋白表达均增强。此外，给予齐留通可抑制AA/5-LOX途径，并逆转转氨酶活性和NAS的升高。
AA/5-LOX途径促进NAFLD的进展，齐留通可使其逆转。
