Role Of 5-lipoxygenase Pathway In Nonalcoholic Steatohepatitis

Objectives:To investigate the role of 5-lipoxygenase pathway in Nonalcoholic Steatohepatitis by observing the activation of 5-lipoxygenase pathway in NASH mice,. Methods:ApoE-/- male mice at the age of 8 weeeks (16),were randomized into two groups:control group (normal diet) and NASH model group (high-fat high-cholesterol diet). All animals were sacrificed after 12 weeks feeding.Body weight, liver weight, liver function and lipid metabolism were measured. Histology of liver were evaluated after HE staining, oil red O staining. Immunohistochemical staining were used to detect PMNs、KCs、LCs in liver.Gene expression levels were examined by Quantitative RT-PCR, the protein level of 5-LO was detected by Western blot,and the leukotriene B4 (LTB4) in the liver tissue were measured by ELISA. Results:Compared with the control group, body weight of mice in the NASH model group was significantly higher (P<0.01),as well as Glu,ALT and TC (P<0.01). Liver Oil red O staining area, density were stronger in NASH model group than control group,HE staining showed that steatosis and inflammatory lesions in NASH model group. At week 16,75% mice in NASH group reached diagnostic criteria for NASH (NAS>4).The expression of 5-LO at mRNA and protein level in the NASH model group were obviously higher than those in the control group, so was the LTB4 in the liver lysate(71.09±18.23 vs 46.71±11.71) and the expression of BLT1 at mRNA level. In addition,the expression of MIP2,CXCR2 and ICAM1,VCAM1 at mRNA levels were higher than those in the control group. Conclusion:1) Mice fed with HFHC diet developed typical NASH features compared to those fed with normal diet, demonstrating the successful establishment of the model; 2) The 5-LO-LTB4-BLT1 pathway is activated and MIP2,CXCR2 and ICAM1,VCAM1 expression were upregulated, which may lead to the invasion of PMNs, there by participating the progress of NASH pathology.