Department of Urology, Bagcilar Training and Research Hospital, Merkez Mah., Dr. Sadik Ahmet Cad., Bagcilar, Istanbul, Turkey.
Department of Pathology, Bagcilar Training and Research Hospital, Bagcilar, Istanbul, Turkey.
Urolithiasis. 2022 Feb;50(1):103-112. doi: 10.1007/s00240-021-01287-x. Epub 2021 Nov 15.
Although the efficacy of extracorporeal shock wave lithotripsy (ESWL) has been well established within the literature, debate continues on the safety of the procedure while focusing on cellular injury and its long-term consequences. Here, we describe the role of neutrophil elastase (NE) in ESWL-related rat kidney damage and investigate the protective effects of sivelestat, an inhibitor of NE, during the early and late phases. Four groups including control, ESWL alone, ESWL with sivelestat 50 mg/kg and ESWL with treatment of 100 mg/kg, each consisting of ten rats were created. Biochemical parameters of kidney function and damage and immunohistopathological findings were compared in the early (72 h after ESWL) and late (1 week after ESWL) periods between the groups. During the early period, serum and urine creatinine levels and urine kidney injury molecule-1 (KIM-1) levels and the KIM-1/creatinine ratio increased in rats treated with ESWL compared to the control group. Furthermore, increased tissue inflammation, ductal dilatation and hemorrhage, and glomerular, tubular, and interstitial damage with increased NE staining were also detected in the ESWL treatment group. During the late phase, although urine KIM-1 levels remained stable at high levels, other parameters showed significant improvements. On the other hand, the administration of sivelestat 50 mg/kg decreased serum creatinine and urine KIM-1 and KIM-1/creatinine levels significantly in rats treated with ESWL, during the early and late periods. Significant decreases in tissue inflammation, tubular, and interstitial tissue damage were also observed during the early period. In conclusion, ESWL-related kidney tissue damage occurs primarily during the early period, and NE is involved in this process. On the other hand, the NE inhibitor sivelestat attenuated this ESWL-induced kidney damage.
尽管体外冲击波碎石术 (ESWL) 的疗效在文献中得到了很好的证实，但关于该手术的安全性仍存在争议，主要集中在细胞损伤及其长期后果上。在这里，我们描述了中性粒细胞弹性蛋白酶 (NE) 在 ESWL 相关大鼠肾损伤中的作用，并研究了 NE 抑制剂西维来司他在早期和晚期阶段的保护作用。创建了包括对照组、单独 ESWL 组、ESWL 加西维来司他 50mg/kg 组和 ESWL 加 100mg/kg 治疗组在内的四组，每组各有十只大鼠。在早期（ESWL 后 72 小时）和晚期（ESWL 后 1 周），比较各组之间肾功能和损伤的生化参数以及免疫组织病理学发现。与对照组相比，接受 ESWL 治疗的大鼠血清和尿液肌酐水平以及尿液肾损伤分子-1 (KIM-1) 水平和 KIM-1/肌酐比值在早期升高。此外，还在 ESWL 治疗组中检测到组织炎症、导管扩张和出血以及肾小球、肾小管和间质损伤增加，同时 NE 染色增加。在晚期，尽管尿液 KIM-1 水平仍保持高水平，但其他参数显示出显著改善。另一方面，在早期和晚期，西维来司他 50mg/kg 的给药显著降低了接受 ESWL 治疗的大鼠的血清肌酐和尿液 KIM-1 和 KIM-1/肌酐水平。还观察到早期组织炎症、肾小管和间质组织损伤显著减少。总之，ESWL 相关的肾组织损伤主要发生在早期，NE 参与了这一过程。另一方面，NE 抑制剂西维来司他减轻了这种 ESWL 引起的肾损伤。
