Anwulignan alleviates IRI by the activation of Nrf2/HO-1 signaling pathway and inhibiting NLRP3-caspase-1-GSDMD-mediated pyroptosis in rats.

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY Tissue & cell Pub Date : 2025-04-01 Epub Date: 2025-02-06 DOI:10.1016/j.tice.2025.102775

Xin Wang, Shihui Wu, Yuxin Jiang, Zihao Yuan, Jian Liu, Shu Jing, Jiale Liu, Jinghui Sun, Chunmei Wang, Dan Wang, He Li

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Abstract

Ischemia/reperfusion injury (IRI) is caused by the reduced blood flow and oxygen level due to the renal artery blockage. The effect of Schisandrae Sphenantherae Fructusandra fruit anwulignan (AN) on the renal IRI injury in rats was investigated. Four rat (Male SD) groups were set, including sham, IRI, sham+AN and IRI+AN groups. This experiment confirmed that AN could reduce renal IRI injury by detecting some biomarkers such as Cre, BUN, LDH, HIF-1α, KIM-1, NGAL, and AIM, which showed decreased levels. AN could increase GSH, CAT, T-AOC, and SOD levels, and decrease MDA and ROS levels in rat kidney tissue, demonstrating that AN can improve oxidative stress damage. In addition, AN diminished the total quantity of TNF-α, IL-1β, IL-6, IL-8, and IL-18 in the renal tissue of rats. In rats with renal IRI, the contents of p-Nrf2 and HO-1 proteins engaged in the Nrf2/HO-1 antioxidant controlled system were increased, and the expression level of Keap1 was diminished. NLRP3, ASC, Caspase-1, GSDMD, GSDMD-N, IL-18, and IL-1β protein levels in kidney tissues decreased significantly in AN group. The results indicate that AN can alleviate renal IRI by reducing the oxidative stress damage via activating the Nrf2/HO-1 signaling pathway and inhibiting NLRP3-Caspase-1-GSDMD-mediated pyroptosis in rats.

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anwuligan通过激活Nrf2/HO-1信号通路，抑制nlrp3 -caspase-1- gsdmd介导的大鼠焦亡，减轻IRI。

缺血再灌注损伤（Ischemia/reperfusion injury， IRI）是由于肾动脉阻塞导致血流量和氧水平降低而引起的。研究五味子安乌里木素对大鼠肾IRI损伤的影响。设大鼠（雄性SD） 4组，分别为sham组、IRI组、sham+AN组和IRI+AN组。本实验通过检测Cre、BUN、LDH、HIF-1α、KIM-1、NGAL、AIM等生物标志物，证实AN可减轻肾IRI损伤，其水平均有所降低。AN可提高大鼠肾组织GSH、CAT、T-AOC和SOD水平，降低MDA和ROS水平，表明AN可改善氧化应激损伤。此外，AN可降低大鼠肾组织中TNF-α、IL-1β、IL-6、IL-8、IL-18的总量。在肾IRI大鼠中，参与Nrf2/HO-1抗氧化控制系统的p-Nrf2和HO-1蛋白含量升高，Keap1表达水平降低。AN组肾组织中NLRP3、ASC、Caspase-1、GSDMD、GSDMD- n、IL-18、IL-1β蛋白水平显著降低。结果表明，AN可通过激活Nrf2/HO-1信号通路，抑制nlrp3 - caspase -1- gsdmd介导的大鼠焦亡，从而减轻大鼠肾IRI的氧化应激损伤。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.