Preventive Effects Of ω-3 Polyunsaturated Fatty Acids From Seal Oil On Mice With Nonalcoholic Fatty Liver

Objectives:Recently, with the changes of diet and life style, the prevalence of nonalcoholic fatty liver disease(NAFLD) is increasing gradually, catching more and more attention. Although the study of its pathog-enesis has achieved great progress, but there is still few effective drugs for the treament. This study aims to investigate the effects and pathways ofω-3 Polyun-saturated Fatty Acids in preventing NAFLD,and to provide a theoretical basis for clinical treatment of non-alcoholic fatty liver disease.Methods:After 72hours exposing in the SPF condition,40 male c57BL/ 6 J mice were divided into three groups randomly with 10 in each group: high-dose group, low-dose group, model group and the normal group; We used high-fat diet, Liber-Decarli liquid to make NAFLD model,which containing 71% fat,18% protein,11% carbohydrate. The model group fed with the high-fat diet(drink freely from the bottles), the high-dose group fed with high-fat diet(the same as model group), seal oil 0.3ml daily,the low-dose group fed with high-fat diet(the same as model group), seal oil 0.15ml daily,and the normal group fed with common diet. Five weeks later,all rats were sacrificed to get their serum and liver tissues.Levels of seral-amino-transferase and lipid were detected.The pathology of liver was observed by HE stain. Heptic cytochrome P4502E1 (CYP2E1) and peroxisome proliferator activatied receptor-α(PPAR-α) were detected by immunohistochemistry. The experimental data between both groups was compared by One-Way ANOVA, while ranked data was adopted with rank sum test.Results:1. Pathology observed by HE stain:①The level of steatosis:Steatosis was not seen in normal group, while in model group, liver cells occurred steatosis generally, the severity of fat degeneration was significantly worse compared with normal group(P<0.05). Compared with model group,steatosis significant relieved in both of the treatment group (P<0.05).②The level of inflammation: no inflammation cell infiltrated in normal group, while portal inflammation occurred in hepatic lobule of model group, with the higher score of inflam-mation activity than normal group (P＜0.05), In addition, the inflammation activity was remarkably slighter in both of the treatment group than in model group (P＜0.05).2. Effect on serum aminotransferase:ALT and AST(IU/L):ALT and AST level (u/L) of model group (29.15±4.02,80.71±5.57 respectively) were increased significantly compared with normal group (9±3.8,51.77±16.59)(P均< 0.01, respectively). Compared with model group, the treatment group (high-dose group:10.2±4.45,47.5±7.55respectively,low-dose group:20.2±1.34,65.17±6.55respectively) were decreased markedly (P< 0.05 respectively). And compared with low-dose group, ALT and AST in the high-dose group were decreased markedly(P< 0.05).3. Effect on serum and liver tissue lipid, blood glucose:①TG and TC(mmol/l):TG and TC level (u/L) of model group (1.38±0.40,4.79±0.71 respectively) were increased significantly compared with normal group (0.55±0.12,34±0.44)(P< 0.01 respectively).Compared with model group, the treatment group (high-dose group:0.5±0.12,2.75±0.47 respectively,lo-w-dose group:0.85±0.81,3.30±0.41 respectively) were decreased marke-dly (P< 0.05 respectively). Compared with low-dose group, the levels in high-dose group were decreased markedly(P< 0.05).②liver tissue TG and TC(mmol/l): Compared with normal group(70.63±19.67,54.27±33.55),the level of model group increased significantly(P< 0.01 respectively).TG a-nd TC level of treatment group (high-dose group:103.58±33.28,52.17±20.24respectively, low-dose group:182.88±65.65,79±19.84respectively) were de-creased mar-kedly (P<0.05 respectively), compared with model group(260.19±90.78,123.7±32.15), And compared with low-dose group,the high-dose group were decreased markedly(P< 0.05 respectively).③GLU(mmol/l):GLU in model group and the two treatment groups increased significa-ntly,compared with the nomal group(8.1±1.19) (P< 0.01 respectively), whi-le compared with model group (11.74±1.43), the treatment groups (high-do-se group:10.55±2.22, low-dose group:11.6±2.91),there was no difference among them (P>0.05 respectively)..4.Effect on Cytokines:①Adiponectin(mmol/l):model group (7.27±3.45) were decreased significantly compared with normal group (21.68±2.3) (P< 0.01), Compared with model group, the treatment group (high-dose group: 12.14±0.83, low-dose group:9.33±0.45) were increased markedly (P< 0.05 respectively). And compared with low-dose group, the high-dose group were increased markedly(P< 0.05).②CYP2E1 and PPAR-a:CYP2E1:Compared with model group, the treatment group were decreased markedly (P< 0.05 respectively), PPAR-a:Compared with model group, the treatment group were increased significantly (P< 0.05 respectively).Conclusion:1.ω-3 Polyunsaturated Fatty Acids of seal oil can strikingly allev-iate hepatic steatosis and NASH. It is an effective medicine in the treatm-ent of NAFLD.2. The preventive effects of seal oil on NAFLD maybe by means of the intervention in cytokines of Adiponectin, CYP2E1 and PPAR-α.