Translational Medicine, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil.
Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Nephrology Division, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil.
Life Sci. 2020 Aug 1;254:117787. doi: 10.1016/j.lfs.2020.117787. Epub 2020 May 14.
To evaluate the effects of esculin treatment on P2X7 receptor and mitochondrial dysfunction in the renal cortex of diabetic rats.
Male Wistar rats, 7 weeks old, were unilaterally nephrectomized. Part of these animals were induced to diabetes using streptozotocin (60 mg/kg). Diabetes was confirmed 48 h after induction, with blood glucose levels ≥200 mg/dL. Part of control and diabetic animals were selected to receive daily doses of esculin (50 mg/kg), during 8 weeks. The animals were placed in metabolic cages at the eighth week of protocol for 24 h urine collection and a small aliquot of blood was collected for biochemical analysis. After this procedure, the animals were euthanized and the remaining kidney was stored for histopathological analysis, Western blotting and mitochondrial high-resolution respirometry.
Although esculin did not change metabolic parameters, renal biochemical function, neither TBARS in DM rats, esculin reduced P2X7 levels in these animals and restored mitochondrial function via glycolysis substrates and β-oxidation. Besides, at the histological analysis, we observed that esculin reduced inflammatory infiltrates and collagen IV deposits as compared to diabetic group.
Esculin attenuated the development of renal injuries caused by hyperglycemia, proinflammatory and oxidative mechanisms mediated by P2X7 receptor, as seen by histological findings and improved mitochondrial function in diabetic animals. This suggests that esculin could be used as an adjuvant therapy to prevent the diabetic nephropathy.
评估七叶皂苷治疗对糖尿病大鼠肾皮质 P2X7 受体和线粒体功能障碍的影响。
7 周龄雄性 Wistar 大鼠行单侧肾切除术。部分动物用链脲佐菌素（60mg/kg）诱导糖尿病。诱导后 48h 血糖水平≥200mg/dL 确认糖尿病。部分对照和糖尿病动物接受每日 50mg/kg 七叶皂苷治疗，持续 8 周。第 8 周方案时，动物置于代谢笼中收集 24h 尿液，采集一小部分血液进行生化分析。在此操作后，动物安乐死，其余肾脏用于组织病理学分析、Western blot 和线粒体高分辨率呼吸测定。
尽管七叶皂苷未改变代谢参数、肾生化功能和糖尿病大鼠的 TBARS，但它降低了这些动物的 P2X7 水平，并通过糖酵解底物和β-氧化恢复了线粒体功能。此外，组织学分析显示，与糖尿病组相比，七叶皂苷减少了炎症浸润和胶原 IV 沉积。
七叶皂苷通过 P2X7 受体介导的高血糖、促炎和氧化机制减轻了肾损伤的发展，改善了糖尿病动物的线粒体功能。这表明七叶皂苷可作为辅助治疗用于预防糖尿病肾病。
