目的：探究橙皮苷对自发性糖尿病小鼠肾脏损伤的保护作用。方法：24周龄db/m小鼠作为对照组，同周龄db/db小鼠随机分为模型组和橙皮苷（200 mg?kg-1）给药组。给药14周后检测各组小鼠血浆中血糖、肌酐浓度，检测尿液中白蛋白、肌酐浓度并计算白蛋白/肌酐值（ACR）。采用H&E染色检测肾脏皮质的形态学变化；PAS染色检测肾小球系膜增生和基底膜增厚变化；免疫荧光检测肾小球巨噬细胞标记抗原（F4/80）变化；RT-PCR检测F4/80、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)基因表达变化。结果：橙皮苷能够减少db/db小鼠尿微量白蛋白排泄；改善肾脏组织结构完整性，降低肾脏巨噬细胞浸润；抑制肾小球系膜增生及基底膜增厚病理改变；显著下调肾脏中F4/80、TNF-α和IL-6基因表达，抑制肾脏组织的炎症反应。结论：橙皮苷具有改善自发性糖尿病小鼠肾脏滤过功能的药效。其作用机制与能够降低肾脏巨噬细胞浸润和下调F4/80、TNF-α以及IL-6基因表达有关。

Objective: This research was aimed to investigate the therapeutic effects of hesperidin in spontaneous diabetic mice induced renal injury. Methods: 24-weeks -old male db/m mice and db/db mice were allocated to normal group, model group and hesperidin treatment group respectively. After treatment with hesperidin (200 mg×kg-1 × day-1, p.o.) 14 weeks, plasma glucose, creatinine, urinary albumin of each group were determined and evaluated albumin/creatinine ratio (ACR). Histomorpholoy inspection of renal cortex were performed after hematoxylin and eosin staining (H&E). The mesangial hyperplasia and basement membrane thickening changes were assessed after periodic acid- schiff (PAS) staining. The aglomerular macrophage infiltration were immunofluorescent stained for F4/80. Renal mRNA expression of F4/80, tumor necrosis factor -α (TNF-α) and interleukin 6 (IL-6) were performed using real-time (RT-PCR). Results: Urinary microalbumin excretion was decreased after hesperidin treatment. Hesperidin treatment also inhibited mesangial hyperplasia, basement membrane thickening and improved the integrity of renal tissue structure.Moreover, hesperidin attenuated the renal inflammation through reducing renal macrophage infiltration and decreasing the mRNA expression of macrophage secreted inflammatory cytokines (TNF-α, IL-6). Conclusion: Hesperidin has a therapeutic effect on renal filtration in spontaneously diabetic mice.The mechanism is related with its ability to reduce renal macrophage infiltration and down-regulation of F4 / 80, TNF-α and IL-6 gene expression.

广东省科技厅国际合作项目（广东省科技厅国际合作基地建设）（2016 B050501003）：代谢病中西医结合防治国际合作基地建设，负责人：郭姣。