抑制细胞焦亡可减轻氧嗪酸钾和尿酸单钠诱导的小鼠痛风性关节炎。
Pyroptosis inhibition alleviates potassium oxonate- and monosodium urate-induced gouty arthritis in mice.
机构信息
Department of Orthopaedics, General Hospital of Northern Theater Command, Shenyang, China.
出版信息
Mod Rheumatol. 2022 Jan 5;32(1):221-230. doi: 10.1080/14397595.2021.1899569.
OBJECTIVES
Pyroptosis has been found implicated in several diseases, however, whether it was involved in gouty arthritis remained unclear. Our study was performed to uncover the role of pyroptosis in gouty arthritis based on a mice model.
METHODS
Mouse gouty arthritis model was established by injections of potassium oxonate (PO), monosodium urate (MSU) and pyroptosis suppressor disulfiram. The diameter of the ankle joints was measured, and ankle joints morphology was observed with hematoxylin-eosin (H&E) staining. Uric acid, creatinine and blood urea nitrogen (BUN) concentrations were measured, while cytokines level and xanthine oxidase (XOD) activity were quantified. Relative pyroptosis markers expressions were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed.
RESULTS
In mouse model, PO and MSU injections cause damage to right ankle, increase the root thickness ratio and uric acid, creatinine and BUN levels in serum and decrease the uric acid and creatinine levels in urine. Also, under PO and MSU treatment, up-regulated XOD activity, inflammatory cytokines levels and pyroptosis markers expressions are observed. Negative regulation of mice injury by disulfiram treatment is also observed.
CONCLUSION
Pyroptosis inhibition might alleviate PO- and MSU-induced gouty arthritis, providing possible therapeutic strategies for gouty arthritis.
目的
细胞焦亡已被发现在多种疾病中起作用，然而，其是否参与痛风性关节炎尚不清楚。本研究通过建立小鼠模型，旨在探讨细胞焦亡在痛风性关节炎中的作用。
方法
通过向小鼠踝关节注射氧嗪酸钾（PO）、单钠尿酸盐（MSU）和细胞焦亡抑制剂二硫化四乙基秋兰姆（disulfiram）构建小鼠痛风性关节炎模型，测量踝关节直径，苏木精-伊红（H&E）染色观察踝关节形态学变化，检测血清尿酸、肌酐和血尿素氮（BUN）浓度，定量检测细胞因子水平和黄嘌呤氧化酶（XOD）活性，采用实时定量聚合酶链反应（qRT-PCR）和 Western blot 检测相关焦亡标志物的表达。
结果
在小鼠模型中，PO 和 MSU 注射会导致右踝关节损伤，增加踝关节根部厚度比和血清尿酸、肌酐和 BUN 水平，并降低尿液中尿酸和肌酐水平。此外，在 PO 和 MSU 处理下，XOD 活性、炎症细胞因子水平和焦亡标志物的表达上调。二硫化四乙基秋兰姆对小鼠损伤的负调控作用也被观察到。
结论
细胞焦亡抑制可能缓解 PO 和 MSU 诱导的痛风性关节炎，为痛风性关节炎提供了潜在的治疗策略。
Zotero 插件