Wang Xin, Wu Shihui, Jiang Yuxin, Yuan Zihao, Liu Jian, Jing Shu, Liu Jiale, Sun Jinghui, Wang Chunmei, Wang Dan, Li He
College of Pharmacy, Beihua University, Jilin, China.
Jilin Hospital of Integrated Traditional Chinese and Western Medicine, Jilin, China.
Tissue Cell. 2025 Apr;93:102775. doi: 10.1016/j.tice.2025.102775. Epub 2025 Feb 6.
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.
缺血/再灌注损伤（IRI）是由肾动脉阻塞导致的血流和氧水平降低引起的。研究了五味子南五味子果实中的安五脂素（AN）对大鼠肾IRI损伤的影响。设置了四组大鼠（雄性SD大鼠），包括假手术组、IRI组、假手术+AN组和IRI+AN组。本实验通过检测一些生物标志物如肌酐（Cre）、尿素氮（BUN）、乳酸脱氢酶（LDH）、缺氧诱导因子-1α（HIF-1α）、肾损伤分子-1（KIM-1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和天冬氨酸氨基转移酶（AIM），证实AN可减轻肾IRI损伤，这些生物标志物水平降低。AN可提高大鼠肾组织中谷胱甘肽（GSH）、过氧化氢酶（CAT）、总抗氧化能力（T-AOC）和超氧化物歧化酶（SOD）水平，并降低丙二醛（MDA）和活性氧（ROS）水平，表明AN可改善氧化应激损伤。此外，AN可减少大鼠肾组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和白细胞介素-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蛋白含量增加，Kelch样ECH相关蛋白1（Keap1）的表达水平降低。AN组肾组织中NLRP3、凋亡相关斑点样蛋白（ASC）、半胱天冬酶-1（Caspase-1）、gasdermin D（GSDMD）、GSDMD-N、IL-18和IL-1β蛋白水平显著降低。结果表明，AN可通过激活Nrf2/HO-1信号通路减轻氧化应激损伤，并抑制NLRP3-Caspase-1-GSDMD介导的大鼠细胞焦亡，从而减轻肾IRI。
