亚慢性溴氰菊酯暴露诱导小鼠肝脏脂质代谢紊乱的作用研究

Effects of deltamethrin subchronic exposure on inducing hepatic lipid metabolism disorder in mice

  • 摘要:
    目的 探究溴氰菊酯(DM)亚慢性暴露对雄性小鼠肝脏脂质代谢的影响。
    方法 选取8周龄SPF级雄性C57BL/6J小鼠18只,随机分为对照组(纯玉米油)、DM低剂量(2.25 mg/kg)组和DM高剂量(9.0 mg/kg)组,连续灌胃90 d。采用苏木精—伊红(HE)染色和Masson染色观察肝脏病理形态变化。检测肝脏中丙氨酸氨基转氨酶(ALT)、天冬氨酸转氨酶(AST)、超氧化物歧化酶(SOD)活性及总胆固醇(T-CHO)、甘油三酯(TG)、还原型谷胱甘肽(GSH)、丙二醛(MDA)水平。采用western blotting法检测与脂质合成相关的甾醇调节元件结合蛋白-1c(SREBP-1c)和与脂质分解相关的过氧化物酶体增殖物激活受体α(PPARα)表达水平。
    结果 与对照组相比,DM高剂量组小鼠体质量、白色脂肪系数显著增加(P<0.05)。HE染色显示,DM高剂量组肝脏组织出现少量炎症细胞聚集;Masson染色显示,DM各剂量组未见明显纤维化改变。DM低、高剂量组肝脏ALT活性升高,DM高剂量组AST活性升高(均P<0.05);与对照组相比,DM高剂量组细胞氧化应激水平显著增加(P<0.05);与对照组相比,DM高剂量组肝脏T-CHO和TG水平升高(P<0.05)。DM各剂量组SREBP-1c表达上调,PPARα表达下调(均P<0.05)。
    结论 亚慢性DM暴露可诱导小鼠肝脏脂质代谢紊乱,可能与氧化应激及脂质合成—分解失衡有关。

     

    Abstract:
    Objective To investigate the effects of deltamethrin (DM) subchronic exposure on hepatic lipid metabolism in male mice.
    Methods Eighteen specific pathogen-free (SPF) male C57BL/6J mice (8-week-old) were randomly assigned to a control group (pure corn oil), a low-dose DM group (2.25 mg/kg), and a high-dose DM group (9.0 mg/kg), followed by oral gavage for 90 consecutive days. Hepatic morphological changes were observed via hematoxylin-eosin (HE) staining and Masson staining. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and superoxide dismutase (SOD), as well as the levels of total cholesterol (T-CHO), triglycerides (TG), reduced glutathione (GSH), and malondialdehyde (MDA) in the liver were measured. Western blotting analysis was performed to detect the expression levels of sterol regulatory elementbinding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor α (PPARα).
    Results Compared with the control group, high-dose DM group showed significantly increased body weight and white adipose coefficient (P < 0.05). HE staining revealed focal inflammatory cell aggregation in liver tissues of high-dose DM group. Masson staining showed no significant fibrosis changes in any of DM dose groups. The liver ALT activity was increased in the low-dose and high-dose DM groups, and the AST activity was increased in the high-dose DM group (all P < 0.05). Compared with the control group, the level of cellular oxidative stress in the high-dose DM group was significantly increased (P < 0.05). Compared with the control group, the levels of hepatic T-CHO and TG in the high-dose DM group were increased (P < 0.05). The expression of SREBP-1c was up-regulated and the expression of PPARα was down-regulated in all DM dose groups (all P < 0.05).
    Conclusion Sub-chronic DM exposure induces hepatic lipid metabolic disorder in mice, possibly through oxidative stress injury and imbalanced lipid synthesis-catabolism.

     

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