Effect of fosinopril on the renal cortex protein expression profile of Otsuka Long-Evans Tokushima Fatty rats
Effect of fosinopril on the renal cortex protein expression profile of Otsuka Long-Evans Tokushima Fatty rats
复制标题
福辛普利对大冢 Long-Evans 德岛肥胖大鼠肾皮质蛋白表达谱的影响。
DOI：
10.3892/etm.2019.8188
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发表时间：
2020-01-01
影响因子：
2.7
通讯作者：
Li, Ping
中科院分区：
文献类型：
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作者：
Li, Zhiguo;Liu, Yeqiang;Li, Ping
血管紧张素转换酶抑制剂（ACEI）可减少尿蛋白排泄，延缓肾功能恶化。然而，肾脏保护的机制尚未完全了解。为探讨ACEI治疗糖尿病肾病（DN）的作用机制，本研究以Long-Evans德岛大冢（LETO）大鼠为对照，观察ACEI福辛普利（FP）对大冢Long-Evans德岛肥胖（OLETF）大鼠肾皮质蛋白表达谱的影响。采用布罗德福德法检测24 h尿蛋白水平。PAS染色观察肾组织病理学变化。在36和56周龄时，使用可溶性和不溶性高分辨率亚蛋白质组学分析方法对OLETF、FP治疗的OLETF和LETO大鼠的肾皮质进行了检查。使用蛋白质印迹分析进一步确认分化的蛋白质。结果表明，FP能显著降低OLETF大鼠肾小球硬化指数和24 h尿蛋白排泄量。此外，FP处理后有17种蛋白质发生显著变化。在这些蛋白质中，应激反应蛋白热休克蛋白A家族成员9和抗氧化剂谷胱甘肽过氧化物酶3的丰度特别增加。提示FP通过抑制氧化应激减轻糖尿病肾损伤。这些差异表达的蛋白质有助于我们进一步了解OLETF大鼠ACEI的作用机制。
Angiotensin-converting enzyme inhibitors (ACEIs) can reduce urinary protein excretion and postpone the deterioration of renal function. However, the mechanisms of renal protection are not yet fully understood. To investigate the mechanisms of ACEIs in the treatment of diabetic nephropathy (DN), the present study determined the effects of the ACEI fosinopril (FP) on the profiling of renal cortex protein expression in Otsuka Long-Evans Tokushima Fatty (OLETF) rats using Long-Evans Tokushima Otsuka (LETO) rats as controls. Urinary protein levels at 24 h were examined using the Broadford method. PAS staining was performed to observe renal histopathological changes. The kidney cortices of OLETF, FP-treated OLETF and LETO rats were examined using soluble and insoluble high-resolution subproteomic analysis methodology at age of 36 and 56 weeks. Differentiated proteins were further confirmed using western blotting analysis. The results demonstrated that FP significantly decreased the glomerulosclerosis index and reduced the 24 h urinary protein excretion of OLETF rats. Additionally, 17 proteins significantly changed following FP-treatment. Amongst these proteins, the abundances of the stress-response protein heat shock protein family A member 9 and the antioxidant glutathione peroxidase 3 were particularly increased. These results indicated that FP ameliorated diabetic renal injuries by inhibiting oxidative stress. In conclusion, the differentially expressed proteins may improve our understanding of the mechanism of ACEIs in the OLETF rats.