Department of Cardiology, The Second Hospital of Hebei Medical University and The Institute of Cardiocerebrovascular Disease of Hebei Province, Shijiazhuang 050000, China.
Biosci Rep. 2020 Feb 28;40(2). doi: 10.1042/BSR20193253.
Contrast-induced acute kidney injury (CI-AKI) is a severe complication caused by intravascular applied radial contrast media (CM). Pyroptosis is a lytic type of cell death inherently associated with inflammation response and the secretion of pro-inflammatory cytokines following caspase-1 activation. The aim of the present study was to investigate the protective effects of acetylbritannilactone (ABL) on iopromide (IOP)-induced acute renal failure and reveal the underlying mechanism. In vivo and in vitro, IOP treatment caused renal damage and elevated the caspase-1 (+) propidium iodide (PI) (+) cell count, interleukin (IL)-1β and IL-18 levels, lactate dehydrogenase (LDH) release, and the relative expression of nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and gasdermin D (GSDMD), suggesting that IOP induces AKI via the activation of pyroptosis. Furthermore, the pretreatment of ABL partly mitigated the CI-AKI, development of pyroptosis, and subsequent kidney inflammation. These data revealed that ABL partially prevents renal dysfunction and reduces pyroptosis in CI-AKI, which may provide a therapeutic target for the treatment of CM-induced AKI.
对比剂诱导的急性肾损伤（CI-AKI）是一种由血管内应用的泛影葡胺（CM）引起的严重并发症。细胞焦亡是一种固有地与炎症反应相关的裂解性细胞死亡方式，并且在 caspase-1 激活后会分泌促炎细胞因子。本研究旨在探讨乙酰britannilactone（ABL）对碘普罗胺（IOP）诱导的急性肾衰竭的保护作用，并揭示其潜在机制。在体内和体外，IOP 处理均会引起肾脏损伤，并增加 caspase-1（+）碘化丙啶（PI）（+）细胞计数、白细胞介素（IL）-1β 和 IL-18 水平、乳酸脱氢酶（LDH）释放以及核苷酸结合域、富含亮氨酸重复蛋白 3（NLRP3）、凋亡相关斑点样蛋白（ASC）和 Gasdermin D（GSDMD）的相对表达，提示 IOP 通过激活细胞焦亡诱导 AKI。此外，ABL 的预处理部分减轻了 CI-AKI、细胞焦亡的发展以及随后的肾脏炎症。这些数据表明，ABL 部分预防了 CI-AKI 中的肾功能障碍和细胞焦亡，这可能为治疗 CM 诱导的 AKI 提供了一个治疗靶点。
