The present study aimed to investigate the interaction between early diabetes and renal IR-induced AKI and to clarify the mechanisms involved. C57BL/6J mice were assigned to the following groups: (1) sham-operated; (2) renal IR; (3) streptozotocin (STZ—55 mg/kg/day) and sham operation; and (4) STZ and renal IR. On the 12th day after treatments, the animals were subjected to bilateral IR for 30 min followed by reperfusion for 48 h, at which time the animals were euthanized. Renal function was assessed by plasma creatinine and urea levels, as well urinary protein contents. Kidney morphology and gene and protein expression were also evaluated. Compared to the sham group, renal IR increased plasma creatinine, urea and albuminuria levels and decreased Nphs1 mRNA expression and nephrin and WT1 protein staining. Tubular injury was observed with increased Havcr1 and Mki67 mRNA expression accompanied by reduced megalin staining. Renal IR also resulted in increased SQSTM1 protein expression and increased proinflammatory and profibrotic factors mRNA expression. Although STZ treatment resulted in hyperglycemia, it did not induce significant changes in renal function. On the other hand, STZ treatment aggravated renal IR-induced AKI by exacerbating renal dysfunction, glomerular and tubular injury, inflammation, and profibrotic responses. Thus, early diabetes constitutes a relevant risk factor for renal IR-induced AKI.

本研究旨在探讨早期糖尿病与肾脏 IR 诱导的 AKI 之间的相互作用，并阐明所涉及的机制。C57BL/6J 小鼠被分配到以下组：（1）假手术；(2)肾IR；（3）链脲佐菌素（STZ—55mg/kg/天）和假手术；(4) STZ和肾IR。在治疗后的第 12 天，对动物进行双侧 IR 30 分钟，然后再灌注 48 小时，此时将动物安乐死。通过血浆肌酐和尿素水平以及尿蛋白含量评估肾功能。还评估了肾脏形态和基因和蛋白质表达。与假手术组相比，肾脏 IR 增加血浆肌酐、尿素和白蛋白水平，降低Nphs1mRNA表达和nephrin和WT1蛋白染色。观察到肾小管损伤，Havcr 1和 Mki 67 mRNA 表达增加，同时巨蛋白染色减少。肾脏 IR 还导致 SQSTM1 蛋白表达增加，促炎和促纤维化因子 mRNA 表达增加。尽管 STZ 治疗导致高血糖，但它并没有引起肾功能的显着变化。另一方面，STZ 治疗通过加剧肾功能不全、肾小球和肾小管损伤、炎症和促纤维化反应来加重肾脏 IR 诱导的 AKI。因此，早期糖尿病构成肾脏 IR 诱导的 AKI 的相关危险因素。