Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
DNA Cell Biol. 2019 Oct;38(10):1134-1142. doi: 10.1089/dna.2019.4732. Epub 2019 Aug 21.
Diabetes mellitus is a complicated metabolic disease characterized by hyperglycemia. Diabetic nephropathy (DN) is a progressive kidney disease, which results in mortality in diabetic patients. The present study was designed to investigate the effect of applying spironolactone (S), captopril (C), and their combination (S+C) on some renal performance indices and microRNAs' (miRNAs) expression. A total of 35 two-month-old male Wistar rats were provided for the study. Intraperitoneal injection of freshly dissolved streptozotocin (60 mg/kg) in cold citrate buffer was used to induce diabetes. Blood samples were examined through calorimetry to assess serum concentrations of glucose, blood urea nitrogen (BUN), and creatinine. To measure the microalbuminuria and transforming growth factor-β (TGF-β) levels and to evaluate the miRNAs expression levels of the kidney tissue, the ELISA method and the real-time PCR were used. The obtained results serve as evidence for the positive relationship between miR-192 and TGF-β levels in the DN rats. A significant increase and decrease were found for miR-29a/b/c and the miR-192 expression of DN after treatment with S, C, and S+C. TGF-β levels and microalbuminuria of diabetic rats also increased. The results obtained from this research study suggest that S, C, and S + C can improve DN by targeting miR-192 and miR-29 family and changing their expression. These findings suggest that miR-192 and miRs-29a/b/c can be potential targets for DN remediation.
糖尿病是一种以高血糖为特征的复杂代谢性疾病。糖尿病肾病（DN）是一种进行性肾病，会导致糖尿病患者死亡。本研究旨在探讨螺内酯（S）、卡托普利（C）及其联合应用（S+C）对某些肾功能指标和 microRNAs（miRNAs）表达的影响。共提供 35 只 2 个月大的雄性 Wistar 大鼠进行研究。用冷柠檬酸缓冲液中新鲜溶解的链脲佐菌素（60mg/kg）进行腹腔注射诱导糖尿病。通过量热法检查血液样本，以评估血清葡萄糖、血尿素氮（BUN）和肌酐浓度。为了测量微量白蛋白尿和转化生长因子-β（TGF-β）水平，并评估肾脏组织的 miRNAs 表达水平，使用 ELISA 方法和实时 PCR 进行了研究。结果表明，DN 大鼠中 miR-192 与 TGF-β水平之间存在正相关。DN 大鼠用 S、C 和 S+C 治疗后，miR-29a/b/c 和 miR-192 的表达显著增加和减少。糖尿病大鼠的 TGF-β水平和微量白蛋白尿也增加。本研究结果表明，S、C 和 S+C 通过靶向 miR-192 和 miR-29 家族并改变其表达，可以改善 DN。这些发现表明，miR-192 和 miR-29a/b/c 可能是 DN 修复的潜在靶点。
