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| 4-辛基衣康酸通过减少肝细胞焦亡减轻脂多糖诱导的小鼠肝损伤 |
| 4-Octoylic itaconate alleviates lipopolysaccharide induced liver injury in mice by reducing hepatocyte pyroptosis |
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| DOI：10.12089/jca.2025.12.013 |
| 中文关键词: 4-辛基衣康酸 脂多糖 细胞焦亡 NOD样受体热蛋白结构域相关蛋白3 消皮素D |
| 英文关键词: 4-Octyl itaconic acid Lipopolysaccharide Cell pyroptosis NOD-like receptor family, pyrin domain containing 3 Gasdermin D |
| 基金项目:荆门市重点科技计划项目（2022YFZD020） |
| 作者 | 单位 | E-mail | | 王婵 | 448000,湖北省荆门市中心医院,荆楚理工学院附属荆门市中心医院麻醉科 | | | 陈杰 | 448000,湖北省荆门市中心医院,荆楚理工学院附属荆门市中心医院麻醉科 | | | 叶晨 | 448000,湖北省荆门市中心医院,荆楚理工学院附属荆门市中心医院麻醉科 | | | 肖伟 | 448000,湖北省荆门市中心医院,荆楚理工学院附属荆门市中心医院麻醉科 | | | 王苗 | 448000,湖北省荆门市中心医院,荆楚理工学院附属荆门市中心医院麻醉科 | | | 刘倩 | 448000,湖北省荆门市中心医院,荆楚理工学院附属荆门市中心医院麻醉科 | | | 杨昌明 | 448000,湖北省荆门市中心医院,荆楚理工学院附属荆门市中心医院麻醉科 | hbjmyangcm@126.com |
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| 中文摘要: |
目的：探索4-辛基衣康酸（4-OI）对脂多糖（LPS）诱导的C57BL/6小鼠肝损伤的影响。
方法：选择雄性C57BL/6小鼠15只，14～16周龄，体重25～30 g。适应性饲养1周后，将小鼠随机分为三组：对照组（C组）、LPS模型组（L组）和4-OI+LPS组（4-OI组），每组5只。4-OI组每天腹腔注射4-OI 50 mg/kg，C组和L组每天给予等容量生理盐水。持续给药1周后，L组和4-OI组腹腔注射LPS 10 mg/kg，6 h后麻醉小鼠，眼眶取血，随后处死小鼠，快速摘取肝脏组织。采用速率法检测血清ALT和AST浓度，ELISA法检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）及白细胞介素-18（IL-18）浓度，Western blot法检测肝脏组织焦亡相关蛋白NOD-样受体蛋白3（NLRP3）、消皮素D（GSDMD）、含半胱氨酸的天冬氨酸蛋白水解酶1（Caspase-1）蛋白含量，HE染色观察肝脏组织病理学变化。
结果：与C组比较，L组和4-OI组血清ALT、AST、TNF-α、IL-6、IL-1β、IL-18浓度明显升高，肝脏组织NLRP3、GSDMD、Caspase-1蛋白含量明显升高（P<0.05）。与L组比较，4-OI组血清ALT、AST、TNF-α、IL-6、IL-1β、IL-18浓度明显降低，肝脏组织NLRP3、GSDMD、Caspase-1蛋白含量明显降低（P<0.05）。C组肝小叶结构正常，肝索呈放射状排列，无充血和炎性细胞浸润，肝细胞边界清晰。L组肝细胞间隙增大，肝索排列发生紊乱，出现炎性细胞浸润。4-OI组肝细胞间隙、肝索结构有所恢复，炎性细胞浸润较少。
结论：4-OI在小鼠脓毒症肝损伤中发挥着明显的抗炎作用，且可有效抑制Caspase-1依赖性的经典焦亡途径，从而减轻脂多糖诱导的小鼠肝损伤。 |
| 英文摘要: |
Objective: To investigate the effect of 4-octyl itaconate (4-OI) on liver injury induced by lipopolysaccharide (LPS) in C57BL/6 mice.
Methods: Fifteen male C57BL/6 mice, aged 14-16 weeks, weighing 25-30 g, were randomly divided into three groups after one week of acclimatization: control group (group C), LPS model group (group L), and LPS + 4-OI group (group 4-OI), 5 mice in each group. Group 4-OI received daily intraperitoneal injections of 4-OI (50 mg/kg), while groups C and L received equal volumes of saline. After one week of treatment, groups L and 4-OI were injected with LPS 10 mg/kg, and all mice were euthanized 6 hours later. Serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) were measured by mteassay. ELISA was used to assess tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and interleukin-18 (IL-18) concentrations in serum. Western blot analysis was performed to evaluate the expression of pyroptosis-related proteins, including NOD-like receptor family, pyrin domain containing 3 (NLRP3), gasdermin D (GSDMD), and cysteine-dependent aspartate-specific protease-1 (Caspase-1) in liver tissue. Liver histopathology was examined via HE staining.
Results: Compared with group C, groups L and 4-OI exhibited significantly elevated ALT, AST, TNF-α, IL-6, IL-1β, and IL-18 levels in serum, along with increased hepatic NLRP3, GSDMD, and Caspase-1 protein expression in liver tissue (P < 0.05). Compared to group L, group 4-OI showed significantly reduced ALT, AST, TNF-α, IL-6, IL-1β, and IL-18 levels in serum, as well as decreased NLRP3, GSDMD, and Caspase-1 expression in liver tissue (P < 0.05). Group C displayed normal hepatic lobule structure with orderly arranged hepatocyte cords, no congestion, and no inflammatory infiltration. Group L exhibited enlarged hepatocyte gaps, disordered hepatic cord arrangement, and inflammatory infiltration, whereas group 4-OI showed improved hepatocyte structure and reduced inflammation.
Conclusion: 4-OI exerts significant anti-inflammatory effects in LPS-induced septic liver injury and attenuates liver damage by suppressing the Caspase-1-dependent canonical pyroptosis pathway． |
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