贻贝多糖对高脂饮食诱导的载脂蛋白E基因敲除小鼠非酒精性脂肪肝的改善作用

于温温; 张金华; 刘云娜; 刘飞; 邵华荣; 韩冠英

doi:10.13386/j.issn1002-0306.2022030026

贻贝多糖对高脂饮食诱导的载脂蛋白E基因敲除小鼠非酒精性脂肪肝的改善作用

Improvement Effect of Mussel Polysaccharide α-D-Glucan on Non-Alcoholic Fatty Liver Apolipoprotein E Knockout Mice Induced by High Fat Diet

摘要

摘要: 本研究探讨海洋贻贝多糖（mussel polysaccharide α-D-Glucan，MP-A）对高脂饮食（high fat diet，HFD）诱导的载脂蛋白E基因敲除（apolipoprotein E^−/−，ApoE^−/−）小鼠非酒精性脂肪肝（non-alcoholic fatty liver disease，NAFLD）的改善作用。20只C57BL/6J正常小鼠随机分为两组：正常组、正常+MP-A组，20只ApoE^−/−小鼠随机分为两组：模型组、模型+MP-A组，每组10只。ApoE^−/−小鼠喂食高脂饮食诱导NAFLD模型，MP-A灌胃干预后，通过血清和肝脏甘油三酯（triglyceride，TG）、总胆固醇（total cholesterol，TC）水平检测，肝组织病理形态学检查等进行疗效评价，同时考察脂代谢和胆固醇代谢相关受体的mRNA和蛋白表达水平。结果显示，与模型组比较，MP-A灌胃7周后，模型+MP-A组小鼠体重增长率（P<0.05）、血清TG水平（P<0.01）、肝脏TG和TC水平显著降低（P<0.05）。组织形态学显示模型+MP-A组小鼠肝脏脂质液泡显著减少。此外，与模型组比较，模型+MP-A组可显著降低小鼠肝脏脂肪酸合成酶（fatty acid synthase，FAS）的mRNA表达水平（P<0.05），显著上调胆固醇7α-羟化酶（cholesterol 7α-hydroxylase，CYP7A1）的mRNA表达水平（P<0.05）。与模型组比较，模型+MP-A组肝组织法尼酯受体（farnesoid X receptor，FXR）、CYP7A1蛋白表达均显著上调（P<0.05），固醇调节元件结合蛋白-1C（sterol regulatory element-binding protein，SREBP-1C）、FAS蛋白表达均显著降低（P<0.05）。以上结果表明MP-A对肝脏脂质代谢密切相关的FXR-SREBP-1C-FAS信号通路和CYP7A1受体的表达具有显著影响，可抑制肝脏TG的积累，显著改善HFD诱导的NAFLD，具有重要的开发潜力。

Abstract: The aim of this study was to investigate the improvement effect of mussel polysaccharide α-D-glucan (MP-A) on non-alcoholic fatty liver disease (NAFLD) in the high-fat diet (HFD) induced apolipoprotein E knockout (ApoE^−/−) mice. 20 normal C57BL/6J mice were randomly divided into two groups: Normal group, normal+MP-A group, and 20 ApoE^−/− mice were randomly divided into two groups: Model group, model+MP-A group, 10 mice in each group. ApoE^−/− mice were fed with high fat diet to induce the NAFLD model. After MP-A were administered, serum and liver triglyceride (TG) and total cholesterol (TC) levels were detected, and the pathological morphology of liver tissue were evaluated by histopathology. The mRNA levels and protein levels of the receptors related to lipid metabolism and cholesterol metabolism were also measured simultaneously. Results showed that compared with the model group, the mice in the model+MP-A group showed significant decreases in the weight growth rate (P<0.05), serum TG level (P<0.01) as well as the liver TG and TC levels (P<0.05). Histomorphology showed that the lipid vacuoles in the mice liver were significantly reduced in the model+MP-A group. In addition, compared with the model group, model+MP-A group could significantly decreased the mRNA expression level of fatty acid synthase (FAS) in liver tissue (P<0.05), and significantly raised the cholesterol 7α-hydroxylase (CYP7A1) mRNA expression level (P<0.05). Moreover, compared with the model group, the expression of farnesoid X receptor (FXR) and CYP7A1 proteins in the liver tissue of the model+MP-A group were significantly improvements (P<0.05), while the expression of sterol regulatory element-binding protein-1C (SREBP-1C) and FAS proteins were significantly reduced (P<0.05). These results showed that MP-A significantly modulated the FXR-SREBP-1C-FAS signaling pathway and the expression of CYP7A1 receptor, which were closely related to hepatic lipid metabolism. Therefore, MP-A could significantly improve the HFD induced NAFLD and has a great development potential.