粒体自噬
炎症体
化学
氧化应激
标记法
细胞凋亡
分子生物学
生物
自噬
生物化学
受体
作者
Yulin Ding,Shuning Liu,Mengqing Zhang,Meile Su,Bin Shao
出处
期刊:Translational Andrology and Urology
[AME Publishing Company]
日期:2024-01-01
卷期号:13 (1): 25-41
被引量:1
摘要
Background: Irradiation (IR) promotes inflammation and apoptosis by inducing oxidative stress and/or mitochondrial dysfunction (MD). The kidneys are rich in mitochondria, and mitophagy maintains normal renal function by eliminating damaged mitochondria and minimizing oxidative stress. However, whether astragaloside IV (AS-IV) can play a protective role through the mitophagy pathway is not known. Methods: We constructed a radiation injury model using hematoxylin and eosin (HE) staining, blood biochemical analysis, immunohistochemistry, TdT-mediated dUTP nick end labeling (TUNEL) staining, ultrastructural observation, and Western blot analysis to elucidate the AS-IV resistance mechanism for IR-induced renal injury. Results: IR induced mitochondrial damage; the increase of creatinine (SCr), blood urea nitrogen (BUN) and uric acid (UA); and the activation of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome and apoptosis in renal tissue. AS-IV administration attenuated the IR-induced MD and reactive oxygen species (ROS) levels in the kidney; enhanced the levels of mitophagy-associated protein [PTEN-induced putative kinase 1 (PINK1)], parkin proteins, and microtubule-associated protein 1 light 3 (LC3) II/I ratio in renal tissues; diminished NLRP3 inflammasome activation-mediated proteins [cleaved cysteinyl aspartate-specific proteinase-1 (caspase-1), interleukin-1β (IL-1β)] and apoptosis-related proteins [cleaved caspase-9, cleaved caspase-3, BCL2-associated X (Bax)]; reduced SCr, BUN, and UA levels; and attenuated the histopathological alterations in renal tissue. Conversely, mitophagy inhibitor cyclosporin A (CsA) suppressed the AS-IV-mediated protection of renal tissue. Conclusions: AS-IV can strongly diminish the activation and apoptosis of NLRP3 inflammasome, thus attenuating the renal injury induced by radiation by promoting the PINK1/parkin-mediated mitophagy. These findings suggest that AS-IV is a promising drug for treating IR-induced kidney injury.
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