基于2型糖尿病肥胖小鼠模型探究维生素D对脂肪组织铁死亡的影响

Investigating vitamin D's effect on adipose tissue ferroptosis in type 2 diabetic obese mouse models

摘要:

目的 探讨维生素D对2型糖尿病肥胖小鼠脂肪组织铁死亡的影响作用。方法 选择6周龄db/db小鼠，分为维生素D缺乏组（LVD）、维生素D正常组（NVD）、维生素D补充组（HVD），另选择非糖尿病同窝db/m小鼠作为对照组。采用苏木精-伊红染色各组小鼠脂肪组织，生化法检测脂肪组织中铁、谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、丙二醛（MDA）水平，Western blotting检测转铁蛋白受体1（TFR1）、溶质载体家族7成员11（SLC7A11）、谷胱甘肽过氧化物酶4（GPX4）蛋白相对表达量。结果 与对照组相比，LVD组小鼠脂肪细胞体积变大（P <0.05）；与LVD组相比，NVD组和HVD组小鼠脂肪细胞体积均变小（P <0.05）；HVD组细胞排列较整齐，大小较均一。与对照组相比，LVD组小鼠脂肪组织内铁含量、MDA水平均升高（P <0.05），SOD、GSH水平均降低（P <0.05）；与LVD组相比，NVD组和HVD组脂肪组织内铁含量、MDA水平均降低（P <0.05），SOD、GSH水平均升高（P <0.05）。与对照组相比，LVD组脂肪组织GPX4和SLC7A11蛋白相对表达量均降低（P <0.05），TFR1蛋白相对表达量升高（P <0.05）；与LVD组相比，NVD组和HVD组GPX4和SLC7A11蛋白相对表达量均升高（P <0.05），HVD组TFR1蛋白相对表达量降低（P <0.05）。结论 维生素D可能通过SLC7A11/GPX4信号通路改善2型糖尿病肥胖小鼠脂肪组织铁死亡。

Abstract:

Objective To investigate vitamin D's effect on ferroptosis in adipose tissue of type 2 diabetic obese mice.Methods Six-week-old db/db mice were divided into vitamin D-deficient (LVD), normal vitamin D (NVD), and vitamin D-supplemented (HVD) groups. Non-diabetic db/m mice served as controls (NC). Adipose tissues underwent hematoxylin-eosin staining. Iron, glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured biochemically. Western blotting detected transferrin receptor 1 (TFR1), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) protein expression.Results Versus NC group, LVD group showed larger adipocytes (P < 0.05). Versus LVD group, NVD and HVD groups exhibited smaller adipocytes (P < 0.05), with HVD displaying more orderly, uniform cell arrangement. Compared to NC, LVD had higher adipose tissue iron and MDA levels (P < 0.05) but lower SOD and GSH levels (P < 0.05). Versus LVD, NVD and HVD showed reduced iron and MDA (P < 0.05) but elevated SOD and GSH (P < 0.05). LVD had lower GPX4 and SLC7A11 protein expression than NC (P < 0.05), but higher TFR1 expression (P < 0.05). Versus LVD, NVD and HVD showed increased GPX4 and SLC7A11 expression (P < 0.05), while HVD had decreased TFR1 expression (P < 0.05).Conclusion Vitamin D may alleviate adipose tissue ferroptosis in type 2 diabetic obese mice through the SLC7A11/GPX4 signaling pathway.