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凉血活血方抑制铁死亡减轻脓毒症急性肾损伤的实验研究
卓玉珍,杨磊,周旻,巩传勇,张萍,李斯雨,李家瑞
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天津市南开医院,中西医结合急腹症研究所天津 300100;天津市南开医院肾内科天津 300100;天津医科大学临床学院天津 300070
摘要:
目的:观察凉血活血方对脓毒症诱导小鼠急性肾损伤(AKI)的保护作用及机制。方法:15只雄性C57BL/6小鼠,采用盲肠结扎穿刺术(CLP)制备脓毒症AKI小鼠模型,小鼠随机分为3组:假手术组、模型组和凉血活血方组,每组5只。凉血活血方组给予凉血活血方(6 g/kg)连续灌胃2 d(1次/d),假手术组和模型组给予同等剂量生理盐水灌胃,术后24 h麻醉取材。HE染色观察肾组织病理变化。生化法检测小鼠肾组织超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽(GSH)的含量,检测血清肌酐(Scr)和尿素氮(BUN)水平。酶联免疫吸附法(ELISA)检测肾组织炎症因子[白细胞介素(IL)-6、IL-1β、肿瘤坏死因子-α(TNF-α)]水平。Western blotting检测肾组织铁死亡相关蛋白溶质载体家族7成员11(SLC7A11)、谷胱甘肽过氧化物酶4(GPX4)、核因子红细胞2相关因子2(Nrf2)、血红素氧合酶1(HO-1)蛋白水平。结果:凉血活血方可以改善脓毒症小鼠的肾功能损害和肾组织病理损伤,降低肾组织中IL-1β、TNF-α、IL-6等炎症因子水平和MDA含量,同时提高肾组织中SOD、GSH含量及SLC7A11、GPX4、Nrf2、HO-1蛋白水平,差异均有统计学意义(P <0.05)。结论:凉血活血方能够改善脓毒症所致AKI小鼠的肾组织病理损伤和肾功能,其机制可能与抑制肾组织铁死亡有关。
关键词:  凉血活血方  脓毒症  急性肾损伤  铁死亡  核因子红细胞2相关因子2
DOI:10.3969/j.issn.1007-6948.2026.01.023
投稿时间:2025-06-09
基金项目:天津市卫健委中西医结合课题(2023048)
Experimental study on the inhibition of ferroptosis by Liangxue Huoxue decoction to alleviate sepsis-induced acute kidney injury
ZHUO Yu-zhen,YANG Lei,ZHOU Min
Abstract:
Objective To observe the protective effect and mechanism of Liangxue Huoxue decoction on sepsis-induced acute kidney injury (AKI) in mice. Methods Fifteen male C57BL/6 mice were used to establish a sepsis-induced AKI mouse model by cecal ligation and puncture (CLP), and the mice were randomly divided into three groups: sham operation group(Sham group), model group(CLP group), and Liangxue Huoxue decoction group(LXHX group). The LXHX group was received intragastric administration of the Liangxue Huoxue decoction (6 g/kg) once daily for 2 consecutive days. The Sham and CLP group were given the same dose of normal saline by gavage. Samples were collected under anesthesia 24 hours after the operation. The pathological changes of renal tissue were observed by HE staining. The contents of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in mouse renal tissues were detected by biochemical methods. Renal function was assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN) levels. The levels of inflammatory cytokines in renal tissue were detected by enzyme-linked immunosorbent assay (ELISA). Protein expression levels of ferroptosis-related markers (SLC7A11, GPX4), Nrf2, and HO-1 in renal tissue were analyzed by Western blotting. Results  The Liangxue Huoxue decoction can improve renal function impairment and renal tissue pathological damage in septic mice, reduce the levels of inflammatory factors such as IL-1β, TNF-α, and IL-6 and the content of MDA in renal tissue, and simultaneously increase the content of SOD and GSH in renal tissue as well as the protein levels of SLC7A11, GPX4, Nrf2, and HO-1( P <0.05). Conclusion The Liangxue Huoxue decoction can improve the pathological damage of renal tissue and renal function in sepsis-induced AKI. The mechanism may be to exert a protective effect by inhibiting ferroptosis of renal tissue.
Key words:  Liangxue Huoxue decoction  sepsis  acute kidney injury  ferroptosis  nuclear factor erythroid 2-related factor

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