Song Mingjie, Gao Xuan, Kou Ruirui, Liu Na, Ma Xiaomin, Zeng Tao, Zhang Cuili
Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Lixia District, Jinan, Shandong 250012, China.
Experimental Center for Public Health and Preventive Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Lixia District, Jinan, Shandong 250012, China.
Toxicol Res (Camb). 2025 Mar 17;14(2):tfaf036. doi: 10.1093/toxres/tfaf036. eCollection 2025 Apr.
Autoimmune hepatitis (AIH) is an autoimmune disease mediated by abnormal autoimmune. The pathogenesis and pathological manifestation of immune-mediated liver injury, induced by concanavalin A (ConA) in mice, closely parallel those observed in human AIH. However, the sensitivity and stability of mice to ConA vary depending on the strain and sex of the mice. Therefore, this study aimed to compare the sensitivity and stability of Balb/c, C57BL/6J, and ICR mice to ConA-induced acute liver injury. In this study, the mice in ConA group were injected with ConA (15 mg/kg·bw) via tail vein. After 8 h, the blood, liver, and spleen were collected for subsequent analysis. The liver index of Balb/c mice was increased ( < 0.05). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels of male C57BL/6J mice in ConA-treated group were the highest among the three strains of mice, followed by female Balb/c mice ( < 0.05). After ConA challenge, ICR, Balb/c, and C57BL/6J mice (both male and female) appeared markedly inflammatory cell infiltration and hepatocyte necrosis. Furthermore, hemorrhagic necrosis is more severe in females than in males. Lastly, male C57BL/6J and female Balb/c mice had the lowest coefficient of variation in serum ALT, AST, and LDH activities, while female Balb/c mice had the minimum coefficient of variation of the liver index, suggesting that they have good stability to ConA. Altogether, our study found that Balb/c female and C57BL/6J male mice have high sensitivity and good stability to ConA challenge, which were suitable for mimicking the pathology of AIH in humans.
自身免疫性肝炎(AIH)是一种由异常自身免疫介导的自身免疫性疾病。小鼠体内由刀豆蛋白A(ConA)诱导的免疫介导性肝损伤的发病机制和病理表现与人类AIH中观察到的情况密切相似。然而,小鼠对ConA的敏感性和稳定性因小鼠的品系和性别而异。因此,本研究旨在比较Balb/c、C57BL/6J和ICR小鼠对ConA诱导的急性肝损伤的敏感性和稳定性。在本研究中,ConA组小鼠通过尾静脉注射ConA(15 mg/kg·bw)。8小时后,采集血液、肝脏和脾脏用于后续分析。Balb/c小鼠的肝脏指数升高(<0.05)。ConA处理组雄性C57BL/6J小鼠的血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和乳酸脱氢酶(LDH)水平在三种品系小鼠中最高,其次是雌性Balb/c小鼠(<0.05)。ConA攻击后,ICR、Balb/c和C57BL/6J小鼠(雄性和雌性)均出现明显的炎性细胞浸润和肝细胞坏死。此外,雌性的出血性坏死比雄性更严重。最后,雄性C57BL/6J和雌性Balb/c小鼠血清ALT、AST和LDH活性的变异系数最低,而雌性Balb/c小鼠的肝脏指数变异系数最小,表明它们对ConA具有良好的稳定性。总之,我们的研究发现雌性Balb/c小鼠和雄性C57BL/6J小鼠对ConA攻击具有高敏感性和良好稳定性,适合用于模拟人类AIH的病理学。