Department of Pharmacology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Cytokine. 2021 Aug;144:155574. doi: 10.1016/j.cyto.2021.155574. Epub 2021 May 8.
Acute kidney injury (AKI) is an important clinical complication of rhabdomyolysis. The inflammatory processes are involved in the pathogenesis of AKI induced by rhabdomyolysis. Thalidomide is an anti-inflammatory agent that has been used in the treatment of inflammatory disorders. The aim of this study was to investigate the therapeutic effect of thalidomide and its underlying mechanisms on a mouse model of rhabdomyolysis-induced AKI. Mice were injected with a single dose of glycerol (50%, 10 ml/kg, im) to induce AKI, and treated with thalidomide (40 and 80 mg/kg/day, orally) for 2 days. Renal tissue and blood samples were collected for histological and biochemical analysis. In thalidomide treated mice, blood urea nitrogen (BUN) (59.3 ± 19.6 vs. 223 ± 33 mg/dl), plasma creatinine (0.58 ± 0.3 vs. 1.28 ± 0.3 mg/dl), relative kidney weight (0.93 ± 0.13% vs. 1.22 ± 0.1%) and histopathological damage (1.5 ± 0.8 vs. 3.3 ± 1.1 score) were significantly lower as compared to the glycerol group. The results also showed that the levels of malondialdehyde (MDA) (0.13 ± 0.02 vs. 0.2 ± 0.01 µM/mg), myeloperoxidase (MPO) (0.1 ± 0.05 vs. 0.25 ± 0.02 U/mg) and the expression of nuclear factor kappa B (NF-κB) (1.7-fold), NLRP3 inflammasome (1.4-fold) and cyclooxygenase (COX)-2 (3-fold) in renal tissue were significantly lower in thalidomide treated group than those in the glycerol group. Thalidomide treatment resulted in lower renal pro-inflammatory cytokines tumor necrosis factor (TNF)-α (6.7 ± 0.8 vs. 12.3 ± 1.2 ng/ml), interleukin (IL)-1β (3.2 ± 0.5 vs. 5.1 ± 0.3 pg/mg), IL-6 (24.7 ± 2.4 vs. 33 ± 3 pg/mg) and transforming growth factor (TGF)-β1 (0.6 ± 0.17 vs. 1.56 ± 0.24 ng/ml) than those in the glycerol treated mice. In addition the levels of monocyte chemoattractant protein (MCP)-1 (9.5 ± 1 vs. 12.8 ± 1.1 pg/mg) and intercellular adhesion molecule (ICAM)-1 (22.8 ± 7.8 vs. 53.3 ± 5.5 pg/mg) were significantly lower in renal tissue of mice treated with thalidomide as compared to the glycerol treated mice. In conclusion these data revealed that thalidomide may be a potential therapeutic approach against rhabdomyolysis-induced AKI through inhibition of inflammatory responses.
急性肾损伤（AKI）是横纹肌溶解症的一种重要临床并发症。炎症过程参与了横纹肌溶解症引起的 AKI 的发病机制。沙利度胺是一种抗炎药物，已被用于治疗炎症性疾病。本研究旨在探讨沙利度胺对甘油诱导的 AKI 小鼠模型的治疗效果及其潜在机制。小鼠单次肌肉注射甘油（50%，10ml/kg，im）诱导 AKI，并用沙利度胺（40 和 80mg/kg/天，口服）治疗 2 天。采集肾组织和血液样本进行组织学和生化分析。在沙利度胺治疗的小鼠中，血尿素氮（BUN）（59.3±19.6 vs. 223±33mg/dl）、血浆肌酐（0.58±0.3 vs. 1.28±0.3mg/dl）、相对肾重（0.93±0.13% vs. 1.22±0.1%）和组织病理学损伤（1.5±0.8 vs. 3.3±1.1 分）明显低于甘油组。结果还表明，肾组织中丙二醛（MDA）（0.13±0.02 vs. 0.2±0.01µM/mg）、髓过氧化物酶（MPO）（0.1±0.05 vs. 0.25±0.02U/mg）和核因子 kappa B（NF-κB）（1.7 倍）、NLRP3 炎性体（1.4 倍）和环氧化酶（COX）-2（3 倍）的表达水平均明显低于甘油组。沙利度胺治疗导致肾前炎性细胞因子肿瘤坏死因子（TNF）-α（6.7±0.8 vs. 12.3±1.2ng/ml）、白细胞介素（IL）-1β（3.2±0.5 vs. 5.1±0.3pg/mg）、IL-6（24.7±2.4 vs. 33±3pg/mg）和转化生长因子（TGF）-β1（0.6±0.17 vs. 1.56±0.24ng/ml）的水平低于甘油组。此外，与甘油组相比，沙利度胺治疗组肾组织中单核细胞趋化蛋白（MCP）-1（9.5±1 vs. 12.8±1.1pg/mg）和细胞间黏附分子（ICAM）-1（22.8±7.8 vs. 53.3±5.5pg/mg）的水平也明显降低。总之，这些数据表明，沙利度胺可能通过抑制炎症反应成为一种治疗横纹肌溶解症引起的 AKI 的潜在方法。
