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蒙古黄芪多糖对NAFLD大鼠肝脏Nrf-2-ARE信号通路的调控作用研究

Regulation of Nrf-2-ARE Signaling Pathway in Liver of NAFLD Rats by Mongolian Astragalus Polysaccharides

    摘要
  • 摘要: 本研究旨在探究蒙古黄芪多糖(Mongolian astragalus polysaccharides, mAPS)对大鼠(Rattus norregicus)非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)的改善作用及其机制。将50只雄性SD大鼠随机分为5组，即空白对照组(Ctrl组)、蒙古黄芪多糖对照组(mAPS组)、高脂饮食模型组(HFD组)、蒙古黄芪多糖治疗组(HFD+mAPS组)和黄连素阳性药物组(HFD+BER组),构建NAFLD大鼠模型；检测NAFLD大鼠血清血脂相关指标和转氨酶指标；HE染色观察NAFLD大鼠肝脏组织病理学表现；RT-qPCR和Western blot检测NAFLD大鼠肝脏及结肠的Nrf-2-ARE信号通路相关基因的mRNA和蛋白水平。结果表明，mAPS能显著降低NAFLD大鼠血清中三酰甘油(triglyceride, TG)、总胆固醇(total cholesterol, TC)、低密度脂蛋白(low density lipoprotein, LDL)、谷丙转氨酶(alanine aminotransferase, ALT)和谷草转氨酶(aspartate aminotransferase, AST)的水平(P<0.05或P<0.01)。与Ctrl组相比，HFD组大鼠的肝脏出现脂肪空泡和炎性细胞聚集等现象，mAPS可以改善高脂饮食诱导的NAFLD大鼠肝脏损伤。通过RT-qPCR对NAFLD大鼠肝脏核因子E2相关因子2-抗氧化反应元件(nuclear factor-erythroid 2-related factor 2-antioxidant response element, Nrf-2-ARE)信号通路相关基因进行检测发现，与Ctrl组相比，核因子E2相关因子2 (nuclear factor-erythroid 2-related factor 2,Nrf-2)、血红素加氧酶-1(heme oxygenase-1,HO-1)、超氧化物歧化酶(superoxide dismutase,SOD)和谷氨酸半胱氨酸连接酶催化亚基(glutamate cysteine ligase catalytic subunit,GCLC)的mRNA表达在HFD组中显著下降(P<0.01), mAPS治疗后，以上基因的mRNA水平明显增高(P<0.05或P<0.01)。对NAFLD大鼠肝脏和结肠的Nrf-2-ARE信号通路相关基因在蛋白水平进行检测，发现其同mRNA水平结果一致。研究结果说明mAPS可以改善NAFLD大鼠的脂质代谢异常，对NAFLD大鼠的肝脏起到保护作用并改善肝脏组织病理学表现，也可能通过Nrf-2-ARE信号减轻NAFLD大鼠的肝脏和结肠的氧化应激。

     

    Abstract: The aim of this work was to study the improvement effect and mechanism of Mongolian astragalus polysaccharides（mAPS） on non-alcoholic fatty liver disease（NAFLD） in rats（Rattus norregicus）. 50 male SD rats were randomly divided into five groups: control group（Ctrl group）, Mongolian astragalus polysaccharide control group（mAPS group）, model group（HFD group）, Mongolian astragalus polysaccharides treatment group（HFD + mAPS group）, and Berberine positive drug group（HFD + BER group）. NAFLD rat model was constructed. Serum lipid related indicators and transaminase indicators were detected in NAFLD rats. HE staining was used to observe the pathological manifestations of liver tissue in NAFLD rats. RT-qPCR and Western blot were used to detect the mRNA and protein levels of Nrf-2-ARE signaling pathway related genes in the liver and colon of NAFLD rats. The results showed that mAPS could significantly decrease the levels of serum triglyceride（TG）, total cholesterol（TC）, low density lipoprotein（LDL）, alanine ami-notransferase（ALT） and aspartate aminotransferase（AST）（P＜0.05 or P＜0.01） in NAFLD rats. Compared with Ctrl group, fat vacuoles and inflammatory cell accumulation appeared in HFD group. mAPS can improve liver damage induced by high-fat diet in NAFLD rats. RT-qPCR detection of the nuclear factor-erythroid 2-related factor 2-antioxidant response element（Nrf-2-ARE）, nuclear factor-erythroid 2-related factor 2（Nrf-2）, heme oxygenase-1（HO-1）, superoxide dismutase（SOD）, and glutamate cysteine ligase catalytic subunits（GCLC）, showed that the mRNA expression of these genes were significantly decreased in the HFD group, After treatment with mAPS, the mRNA expression of these genes increased significantly（P＜0.05 or P＜0.01）. At the same time, the protein level of Nrf-2-ARE signal pathway in liver and colon of NAFLD rats was detected, and the result was consistent with that of mRNA level. Research results showed that mAPS could improve lipid metabolism abnormalities in NAFLD rats, protect the liver and improve liver histopathological manifestations. mAPS may also alleviate oxidative stress in the liver and colon of NAFLD rats through Nrf-2-ARE signaling.

     

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