Zhenfeng Ye, Jing Zhang, Zhou Xu, Zhangwang Li, Gaomin Huang, Bin Tong, Panpan Xia, Yunfeng Shen, Honglin Hu, Peng Yu, Xiaoqing Xi
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引用次数: 0
摘要
肾缺血再灌注损伤(IRI)诱发的急性肾损伤(AKI)是一种严重的临床症状。ROS 积累、抗氧化途径缺乏和炎症都与 IRI 有关。吡格列酮具有抗炎和抗氧化作用。本研究旨在探讨吡格列酮对IRI诱导的AKI的保护作用。将无病原体的 Sprague-Dawley (SD) 大鼠任意分为四组:假手术组 对照组(CON)、CON + Pio 组、I/R + 盐水组和 I/R + Pio 组。此外,还对 HK-2 细胞进行缺氧和再氧,以建立 H/R 模型,研究 Pio 的保护机制。对模型大鼠进行吡格列酮预处理可降低IRI后的尿素氮和肌酐水平、组织病理学评分和细胞毒性。吡格列酮治疗可明显减轻肾细胞凋亡,降低细胞毒性,增加 Bcl-2 的表达,下调 Bax 的表达。此外,吡格列酮治疗后,I/R大鼠和H/R细胞中的ROS和炎症因子,包括NLRP3、ASC、pro-IL-1β、pro-caspase-1、cleaved-caspase-1、TNF-α、IL-6和IL-1β的水平均恢复正常。吡格列酮通过减轻氧化应激和NLRP3炎性体的激活改善了IRI诱导的AKI。因此,吡格列酮有望成为治疗和预防肾脏IRI的新型药物。
Pioglitazone ameliorates ischemia/reperfusion-induced acute kidney injury via oxidative stress attenuation and NLRP3 inflammasome
Acute kidney injury (AKI) induced by renal ischemia/reperfusion injury (IRI) is a severe clinical condition. ROS accumulation, antioxidant pathways deficiency, and inflammation are involved in IRI. Pioglitazone (Pio) exerts anti-inflammatory and antioxidant effects. The aim of this study was to explore the protective effects of pioglitazone against IRI-induced AKI. Pathogen-free Sprague–Dawley (SD) rats were arbitrarily divided into four groups: Sham operation group Control (CON) group, CON + Pio group, I/R + Saline group, and I/R + Pio group. In addition, HK-2 cells were subjected to hypoxia and reoxygenation to develop an H/R model for investigation of the protective mechanism of Pio. Pretreatment with pioglitazone in the model rats reduced urea nitrogen and creatinine levels, histopathological scores, and cytotoxicity after IRI. Pioglitazone treatment significantly attenuated renal cell apoptosis, decreased cytotoxicity, increased Bcl-2 expression, and downregulated Bax expression. Besides, the levels of ROS and inflammatory factors, including NLRP3, ASC, pro-IL-1β, pro-caspase-1, cleaved-caspase-1, TNF-α, IL-6, and IL-1β, in I/R rats and H/R cells were normalized by the pioglitazone treatment. Pioglitazone improved IRI-induced AKI by attenuating oxidative stress and NLRP3 inflammasome activation. Therefore, pioglitazone has the potential to serve as a novel agent for renal IRI treatment and prevention.
期刊介绍:
Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well.
Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format.
Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.