动物营养学报 >

2021 , Vol. 33 >Issue 7: 4123 - 4132

DOI: https://doi.org/10.3969/j.issn.1006-267x.2021.07.053

实验方法与实验动物 EXPERIMENTAL METHOD AND ANIMAL

微生物源性抗氧化剂对葡聚糖硫酸钠诱发小鼠肝脏氧化损伤和炎症反应的影响

  • 李莉 ,
  • 马升 ,
  • 张京 ,
  • 徐维娜 ,
  • 徐建雄
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  • 上海交通大学农业与生物学院, 上海市兽医生物技术重点实验室, 上海 200240
李莉(1996-),女,江苏扬州人,硕士研究生,研究方向为动物营养调控。E-mail:1597380370@qq.com

收稿日期: 2020-12-16

  网络出版日期: 2021-07-06

基金资助

国家自然科学基金项目（31872367）

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Effects of Microbe-Derived Antioxidants on Oxidative Damage and Inflammatory Response in Liver of Mice Induced by Dextran Sulfate Sodium Salt

  • LI Li ,
  • MA Sheng ,
  • ZHANG Jing ,
  • XU Weina ,
  • XU Jianxiong
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  • Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai 200240, China

Received date: 2020-12-16

  Online published: 2021-07-06

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摘要

本试验旨在探究葡聚糖硫酸钠（DSS）诱导小鼠肝脏损伤以及微生物源性抗氧化剂（MA）的缓解作用及可能机制。试验采用48只6周龄C57BL/6J雄性小鼠，预饲养1周后，随机分为4组，每组12只。对照组和DSS组每天每只小鼠灌胃0.020 mL/g BW的生理盐水，低剂量MA组（LMA组）每天每只小鼠灌胃0.002 mL/g BW的MA，高剂量MA组（HMA组）每天每只小鼠灌胃0.003 mL/g BW的MA。对照组每天饮用双蒸水；其余各组1~7 d饮用双蒸水，8~14 d饮用含3% DSS的双蒸水。试验期14 d。结果表明：1）与对照组相比，DSS组肝脏组织中央静脉汇管区出现炎性细胞浸润，脂肪变性；DSS组肝脏过氧化氢（H2O2）、丙二醛（MDA）含量极显著升高（P<0.01），肝脏总超氧化物歧化酶（T-SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性和谷胱甘肽（GSH）含量及总抗氧化能力（T-AOC）显著或极显著降低（P<0.05或P<0.01），肝脏线粒体膜电位显著降低（P<0.05）。与DSS组相比，MA处理可改善肝脏组织中央静脉汇管区炎性细胞浸润和脂肪变性；LMA组肝脏H2O2含量显著降低（P<0.05），肝脏T-AOC和GSH-Px活性显著升高（P<0.05）；HMA组肝脏H2O2、MDA含量显著降低（P<0.05），肝脏T-SOD、GSH-Px活性和GSH含量及T-AOC显著升高（P<0.05）；LMA组和HMA组肝脏线粒体膜电位显著升高（P<0.05）。2）与对照组相比，DSS组肝脏凋亡相关斑点样蛋白（ASC）、半胱天冬蛋白酶-1（Caspase-1）、白细胞介素-1β（IL-1β）、细胞外调节蛋白激酶（PERK）、活化转录因子6（ATF6）、肌醇依赖性激酶1（IRE1）、葡萄糖调节蛋白78（GRP78）、端粒酶逆转录酶（Tert）mRNA相对表达量显著升高（P<0.05）。与DSS组相比，HMA组ASC、Caspase-1、IL-1β、GRP78 mRNA表达量显著降低（P<0.05）。由此可见，DSS诱发了小鼠肝脏组织氧化应激、损伤和炎症，MA对此有明显的缓解作用，其中高剂量MA的缓解作用更强，并且Nod样受体家族含pyrin结构域蛋白3（NLRP3）炎症小体参与调控炎症过程。

关键词： 微生物源性抗氧化剂; 葡聚糖硫酸钠; 肝脏; 氧化应激; NLRP3

本文引用格式

李莉 , 马升 , 张京 , 徐维娜 , 徐建雄 . 微生物源性抗氧化剂对葡聚糖硫酸钠诱发小鼠肝脏氧化损伤和炎症反应的影响[J]. 动物营养学报, 2021 , 33(7) : 4123 -4132 . DOI: 10.3969/j.issn.1006-267x.2021.07.053

Abstract

This experiment was conducted to explore the dextran sulfate sodium salt (DSS) induced liver damage of mice and the relieving effects and possible mechanism of microbe-derived antioxidants (MA). Forty-eight 6-week-old C57BL/6J male mice were randomly divided into 4 groups with 12 mice in each group after 1 week of pre feeding. Each mouse in the control group and DSS group was given normal saline 0.020 mL/g BW by gavage every day, each mouse in the low-dose MA group (LMA group) was given 0.002 mL/g BW MA by gavage every day, and each mouse in the high-dose MA group (HMA group) group was given 0.003 mL/g BW MA by gavage every day. Mice in the control group drank double distilled water every day; mice in other groups drank double distilled water from 1 to 7 days, and drank double distilled water contained 3% DSS from 8 to 14 days. The experiment lasted for 14 days. 1) compared with the control group, the DSS group showed inflammatory cell infiltration and steatosis in the central venous duct area of liver tissue; the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) in liver were significantly increased (P<0.01), the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content and total antioxidant capacity (T-AOC) in liver were significantly decreased (P<0.05 or P<0.01), and the liver mitochondrial membrane potential was significantly decreased (P<0.05). Compared with the DSS group, the DSS, MA treatment improved the inflammatory cell infiltration and steatosis in the central venous duct area of liver tissue; the liver H2O2 content of LMA group was significantly decreased (P<0.05), and the liver T-AOC and GSH-Px activity were significantly increased (P<0.05); the contents of H2O2 and MDA in liver of HMA group were significantly decreased (P<0.01), and the T-SOD, GSH-Px activities and GSH content and T-AOC in liver were significantly increased (P<0.05); the liver mitochondrial membrane potential of LMA group and HMA group was significantly increased (P<0.05). 2) Compared with the control group, the mRNA relative expression levels of apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartatespecific proteinase-1 (Caspase-1), interleukin-1β (IL-1β), extracellular regulated protein kinases (PERK), activating transcription factor 6 (ATF6), inositol requiring enzyme 1 (IRE1), glucose regulated protein 78 (GRP78) and telomerase reverse transcriptase (Tert) in liver of DSS group were significantly increased (P<0.05). Compared with the DSS group, the mRNA relative expression levels of ASC, Caspase-1, IL-1β and GRP78 in liver of HMA group were significantly decreased (P<0.05). In conclusion, DSS induces oxidative stress, injury and inflammation in liver of mice, MA have a significant alleviating effect on this, the alleviating effect of high-dose MA is stronger, and the Nod-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is involved in regulating inflammation.

Key words： microbe-derived antioxidants; DSS; liver; oxidative stress; NLRP3

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