Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal.
Life Sci. 2019 Oct 1;234:116738. doi: 10.1016/j.lfs.2019.116738. Epub 2019 Aug 6.
Oxidative stress has been linked to the development and progression of diabetic nephropathy (DN). The present study evaluated whether the dipeptidyl peptidase-4 inhibitor sitagliptin attenuates glomerular lesions and oxidative stress evoked by chronic hyperglycemia, by a mechanism independent of insulin secretion and glycemia normalization.
A rat model of DN caused by streptozotocin injection was established and the effects of sitagliptin (5 mg/kg/day) were evaluated after two weeks of treatment.
Sitagliptin treatment did not change body weight, glycemic and lipid profiles. However, histopathological observation revealed that sitagliptin attenuates diabetes-induced glomerular lesions on diabetic rats. Sitagliptin also ameliorated the increase in DPP-4 content and promoted the stabilization of GLP-1 in the diabetic kidney. Furthermore, sitagliptin treatment significantly attenuated the increase of free-radical formation and the decrease of antioxidant defenses, attenuating therefore the oxidative stress in the kidneys of diabetic animals.
The results suggest that sitagliptin treatment alleviates kidney oxidative stress in type 1 diabetic rats, which could play a key role in reducing the progression of DN.
氧化应激与糖尿病肾病（DN）的发生和进展有关。本研究评估了二肽基肽酶-4 抑制剂西他列汀是否通过独立于胰岛素分泌和血糖正常化的机制，减轻慢性高血糖引起的肾小球病变和氧化应激。
建立链脲佐菌素注射诱导的大鼠 DN 模型，并在治疗 2 周后评估西他列汀（5mg/kg/天）的作用。
西他列汀治疗并未改变体重、血糖和血脂谱。然而，组织病理学观察显示，西他列汀可减轻糖尿病大鼠的肾小球病变。西他列汀还改善了 DPP-4 含量的增加，并促进了 GLP-1 在糖尿病肾脏中的稳定。此外，西他列汀治疗显著减轻了自由基形成的增加和抗氧化防御的降低，从而减轻了糖尿病动物肾脏的氧化应激。
研究结果表明，西他列汀治疗可减轻 1 型糖尿病大鼠肾脏的氧化应激，这可能在减少 DN 的进展中起关键作用。
