白细胞介素-33改善ob/ob小鼠糖脂代谢紊乱的作用研究

IL-33 Improves Glucose-Lipid Metabolism Disorders in ob/ob Mice

目的研究白细胞介素-33(IL-33)对ob/ob小鼠糖脂代谢紊乱的作用及其可能机制。方法ob/ob小鼠随机分为模型组和IL-33给药组(每只0.5μg),连续给药4周,每周测定血糖和体重。给药2周后进行腹腔内葡萄糖耐量实验,给药结束后检测血清胆固醇和甘油三酯水平,对肝脏、脂肪、胰腺进行组织学分析,并对脂肪组织炎症因子、脾淋巴细胞Cd73和Cd39的mRNA水平,以及肝脏组织核受体进行检测。结果结果显示,IL-33显著降低ob/ob小鼠血糖、体重,改善葡萄糖耐量,降低血清甘油三酯水平。IL-33减少肝脏组织脂肪聚集,降低脂肪细胞的大小,维持胰岛正常结构。IL-33降低脂肪组织炎症因子Ccl2和Il1a的mRNA水平,提高脾淋巴细胞Cd73和Cd39的mRNA水平。同时,IL-33升高肝脏X受体(LXR)和过氧化物酶体增殖物激活受体(PPARγ)的表达。结论IL-33对糖脂代谢的调节作用可能与改善炎症反应和影响核受体的表达有关。

OBJECTIVE To investigate the effects of cytokine IL-33 on glucose-lipid metabolism disorder and its underlying mechanism.METHODS Ob/ob mice were injected for 4 weeks with IL-33(0.5μg·mice^-1,every other day)or PBS.Body weight and blood glucose were measured weekly.After two weeks,glucose tolerance tests were performed.After administration,histological analyses for liver,fat and pancreatic tissues were performed.The mRNA expression of inflammatory factors in fat tissues,Cd73 and Cd39 in splenic lymphocytes,as well as protein expression of nuclear receptors in liver tissues were detected.RESULTS The results showed that IL-33 decreased body weight and blood glucose,improved glucose tolerance,and reduced serum triglyceride in ob/ob mice.IL-33 reduced lipid accumulation in liver tissues,decreased adipocyte size,and maintained the islet morphology and structural integrity.IL-33 decreased the mRNA expression of Ccl2 and Il1a,whereas increased the expression of Cd73 and Cd39.Further analysis revealed that IL-33 increased expression of nuclear receptors LXR and PPARγ.CONCLUSION The effect of IL-33 on inflammatory response and nuclear receptors might contribute to the improvement of glucose-lipid metabolism in ob/ob mice.