目的 研究榅桲提取物（hydroethanolic extract of Cydonia oblonga Mill.,HECO）对高脂饮食小鼠脂肪肝的改善作用及可能机制。方法 24只C57BL/6J雄性小鼠随机分至正常对照组（CON）、高脂组（HFD）、榅桲提取物干预组（HECO）,后两组采用高脂饲料饲喂,HECO组同时采用200 mg/（kg·d）HECO灌胃。12 w后观察小鼠肝脏病理学形态,测定血脂、肝功能、肝脏脂质及氧化应激标志物、炎症因子、脂代谢相关基因的表达、NF-κB磷酸化水平和Nrf2核转位水平。结果 与HFD组相比,HECO显著降低小鼠体重,抑制肝脏脂肪沉积,增加血清高密度脂蛋白胆固醇（high-density lipoprotein cholesterol,HDL-C）水平,降低甘油三酯（triglycerides,TG）、总胆固醇（total cholesterol,TC）、低密度脂蛋白胆固醇（low-density lipoprotein cholesterol,LDL-C）、天冬氨酸氨基转移酶（aspartate aminotransferase,AST）和丙氨酸氨基转移酶（alanine aminotransferase,ALT）水平（P<0.05）;在降低肝脏TG、TC和游离脂肪酸含量的基础上增加谷胱甘肽过氧化物酶（glutathione peroxidase,GPx）、超氧化物歧化酶（superoxide dismutase,SOD）、过氧化氢酶（catalase,CAT）活性及还原型谷胱甘肽（glutathione,GSH）水平,降低丙二醛（malondialdehyde,MDA）、白介素-1β（interleukin-1β,IL-1β）、白介素-6（interleukin-6,IL-6）和肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）的水平（P<0.05）;下调脂质生成基因Srebp1c、Fasn、Acc1、Scd1的表达,促进脂肪酸转运及氧化相关基因Cpt1α、Fgf21、Cd36和Fabp1的表达（P<0.05）;HECO显著抑制NF-κB的磷酸化,促进Nrf2的核转位（P<0.05）。结论 HECO可通过维持肝脏氧化还原状态,减轻炎症反应,调节脂代谢,发挥防控代谢相关脂肪性肝病的作用。
Abstract
Objective To study the effects of hydroethanolic extract of Cydonia oblonga Mill. (HECO) on fatty liver induced by high fat diet in mice and its potential mechanism. Methods Twenty-four male C57BL/6J mice were randomly assigned to the control group (CON), high-fat diet group (HFD), and HECO intervention group (HECO). The latter two groups were fed with a high-fat diet. HECO group were additionally treated with 200 mg/(kg·d) HECO by oral gavage. The intervention lasted for 12 weeks, followed by liver histology examination, measurements of serum and hepatic lipid levels, hepatic function, as well as the oxidative stress biomarkers, inflammatory cytokines, lipid metabolism genes expression, NF-kB p65 phosphorylation and Nrf2 nuclear translocation. Results Compared with the HFD group, HECO significantly decreased body weight, inhibited hepatic lipid deposition, increased high-density lipoprotein cholesterol level and reduced triglycerides, total cholesterol, low-density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase levels in serum (P<0.05). HECO also significantly decreased hepatic TG, TC and free fatty acid levels, increased the activities of glutathione peroxidase, superoxide dismutase and catalase, and elevated glutathione level. Meanwhile, hepatic MDA, interleukin-1β, interleukin-6, and tumor necrosis factor-α levels were reduced. The expressions of lipogenesis genes, Srebp1c, Fasn, Acc1, and Scd1 were downregulated, and the expressions of fatty acid transport and β oxidation genes, Cpt1α, Fgf21, Cd36 and Fabp1 were upregulated. Additionally, HECO significantly inhibited the phosphorylation of NF-κB and enhanced the nuclear translocation of Nrf2 (P<0.05). Conclusion HECO is effective in preventing metabolic dysfunction-associated fatty liver disease possibly by maintaining hepatic redox status, inhibiting inflammation and improving lipid metabolism.
关键词
脂肪肝 /
榅桲提取物 /
脂质代谢 /
氧化应激 /
炎症反应
Key words
fatty liver /
extract of Cydonia oblonga Mill. /
lipid metabolism /
oxidative stress /
inflammation
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基金
中国博士后基金（No.2017M620191）
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