Acetylbritannilactone attenuates contrast-induced acute kidney injury through its anti-pyroptosis effects
Acetylbritannilactone attenuates contrast-induced acute kidney injury through its anti-pyroptosis effects
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DOI：
10.1042/bsr20193253
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发表时间：
2020-02-18
影响因子：
4
通讯作者：
Cui, Wei
中科院分区：
文献类型：
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作者：
Chen, Fei;Lu, Jingchao;Cui, Wei
造影剂诱导的急性肾损伤（CI-AKI）是血管内应用放射状造影剂（CM）引起的严重并发症。细胞凋亡是一种裂解型细胞死亡，与炎症反应和caspase-1激活后促炎细胞因子的分泌内在相关。本研究旨在探讨乙酰旋覆花内酯（ABL）对碘普罗胺（IOP）诱导的急性肾功能衰竭的保护作用及其机制。在体内和体外，IOP治疗引起肾损伤，并升高caspase-1（+）碘化丙啶（PI）（+）细胞计数、白细胞介素（IL）-1 β和IL-18水平、乳酸脱氢酶（LDH）释放以及核苷酸结合结构域、富含亮氨酸重复序列的蛋白3（NLRP 3）、骨化相关斑点样蛋白（ASC）和gasdermin D（GSDMD）的相对表达，这表明IOP通过焦亡的激活诱导阿基。此外，ABL预处理部分减轻了CI-AKI、焦亡的发展和随后的肾脏炎症。这些数据表明，ABL部分预防CI-AKI中的肾功能不全并减少焦亡，这可能为治疗CM诱导的阿基提供治疗靶点。
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)-1 beta 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.