Ischemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in the aging population. A reduction of hydrogen sulfide (H₂S) production in the old kidney and renal IRI contribute to renal pathology and injury. Recent studies suggest that microRNAs (miRs) play an important role in the pathophysiology of AKI and a significant crosstalk exists between H₂S and miRs. Among the miRs, miR-21 is highly expressed in AKI and is reported to have both pathological and protective role. In the present study, we sought to determine the effects of age-induced reduction in H₂S and mir-21 antagonism in AKI. Wild type (WT, C57BL/6J) mice aged 12–14 weeks and 75–78 weeks underwent bilateral renal ischemia (27 min) and reperfusion for 7 days and were treated with H₂S donor, GYY4137 (GYY, 0.25 mg/kg/day, ip) or locked nucleic acid anti-miR-21 (20 mg/kg b.w., ip) for 7 days. Following IRI, old kidney showed increased macrophage polarization toward M1 inflammatory phenotype, cytokine upregulation, endothelial–mesenchymal transition, and fibrosis compared to young kidney. Treatment with GYY or anti-miR-21 reversed the changes and improved renal vascular density, blood flow, and renal function in the old kidney. Anti-miR-21 treatment in mouse glomerular endothelial cells showed upregulation of H₂S-producing enzymes, cystathionine β-synthase (CBS), and cystathionineγ-lyase (CSE), and reduction of matrix metalloproteinase-9 and collagen IV expression. In conclusion, exogenous H₂S and inhibition of miR-21 rescued the old kidney dysfunction due to IRI by increasing H₂S levels, reduction of macrophage-mediated injury, and promoting reparative process suggesting a viable approach for aged patients sustaining AKI.

缺血再灌注损伤（IRI）是老年人群急性肾损伤（AKI）的常见原因。旧肾和肾 IRI 中硫化氢 (H _{2 S) 产生的减少会导致肾脏病理和损伤。}最近的研究表明，microRNAs (miRs) 在 AKI 的病理生理学中起重要作用，并且 H ₂ S 和 miRs 之间存在显着的串扰。在 miRs 中，miR-21 在 AKI 中高表达，据报道具有病理和保护作用。在本研究中，我们试图确定年龄引起的 H _{2减少的影响}S 和 mir-21 在 AKI 中的拮抗作用。12-14 周和 75-78 周的野生型 (WT, C57BL/6J) 小鼠接受双侧肾缺血（27 分钟）和再灌注 7 天，并用 H ₂ S 供体 GYY4137 (GYY, 0.25 mg/kg /day, ip) 或锁定核酸抗 miR-21 (20 mg/kg bw, ip) 7 天。与年轻肾相比，IRI 后，老年肾的巨噬细胞极化向 M1 炎症表型、细胞因子上调、内皮-间质转化和纤维化增加。用 GYY 或抗 miR-21 治疗可逆转旧肾的变化并改善肾血管密度、血流和肾功能。小鼠肾小球内皮细胞中的抗 miR-21 治疗显示 H _2上调产生 S 的酶、胱硫醚 β-合酶 (CBS) 和胱硫醚γ-裂解酶 (CSE)，以及基质金属蛋白酶 9 和胶原蛋白 IV 表达的减少。总之，外源性 H _{2 S 和 miR-21 的抑制通过增加 H 2} S 水平、减少巨噬细胞介导的损伤和促进修复过程来挽救由 IRI 引起的老年肾功能障碍，这为老年 AKI 患者提供了一种可行的方法。