目的 拟通过比较不同品系小鼠对马兜铃酸I（AAI）的耐受性及急性毒性反应，以期为研究AAⅠ提供借鉴和指导。方法 采用ig给药方式，单次给予C57BL/6和C3H/He小鼠AAⅠ（5.0、9.3、17.1、31.7、58.6、108.4、200.5 mg·kg^-1），每种品系小鼠均设置1个溶媒对照组，并于给药后进行一般症状观察及体质量测定。试验结束进行剖检、脏器称质量、血清生化指标检测及病理学检查。结果 单次给予一定剂量AAⅠ可引起2种品系小鼠出现体质量下降、消瘦、弓背及活动减少，甚至死亡，并且C57BL/6小鼠出现上述改变的AAⅠ剂量低于C3H/He小鼠。C57BL/6小鼠的AAⅠ半数致死量（LD₅₀）为38.07 mg·kg^-1，C3H/He小鼠的AAⅠ LD₅₀为59.92 mg·kg^-1。C57BL/6小鼠AAⅠ最大耐受剂量（MTD）为17.1 mg·kg^-1，C3H/He小鼠的AAⅠ MTD为31.7 mg·kg^-1。给予一定剂量的AAI后，C57BL/6小鼠各项血清生化指标未见改变，而C3H/He小鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、肌酐（CRE）水平升高。AAI可引起C57BL/6、C3H/He小鼠多个脏器出现急性损伤，如胸腺、脾脏、肾脏、肝脏及前胃，并且引起C3H/He小鼠上述组织器官出现组织病理学改变的AAⅠ剂量均低于C57BL/6小鼠。结论 通过对不同剂量AAⅠ所引起C57BL/6和C3H/He小鼠整体毒性、血清生化指标、动物死亡原因以及组织病理学改变分析，认为C3H/He小鼠对AAⅠ的急性毒性比C57BL/6小鼠更加敏感。既验证了AAⅠ致C57BL/6和C3H/He小鼠的急性毒性特点和作用的靶器官，也为研究不同品系小鼠对AAⅠ急性毒性的敏感性和耐受性提供了数据支持。

Objective To compared the tolerance and toxicity of different strains of mice to aristolochic acid I (AAI) to provide a reference and guidance for the study of AAI. Methods C57BL/6 and C3H/He mice were treated with AA Ⅰ by oral gavage. Each strain of mice was assigned one vehicle control and seven AAI dose (5.0, 9.3, 17.1, 31.7, 58.6, 108.4, and 200.5 mg·kg^-1) groups, and clinical symptom observation and weight measurement were performed after dosing. At the end of the experiment, necropsy, organ weighing, serum biochemical index detection, and pathological examination were performed. Results A single administration of a certain dose of AAI caused weight loss, emaciated, arched back, reduced activity, and even death in both strains of mice, and the dosage of AAⅠ in C57BL/6 mice with the above changes was lower than that in C3H/He mice. The AAⅠ median lethal dose (LD₅₀) of C57BL/6 mice was 38.07 mg·kg^-1, and that of C3H/He mice was 59.92 mg·kg^-1. The maximum tolerated dose (MTD) of AAI in C57BL/6 mice was 17.1 mg·kg^-1, and that in C3H/He mice was 31.7 mg·kg^-1. AAI did not induce serum biochemical changes in C57BL/6 mice, while increased levels of ALT, AST, and CRE were found in C3H/He mice. AAI can cause acute injury to multiple organs in C57BL/6 and C3H/He mice, such as the thymus, spleen, kidneys, liver, and forestomach. And the dose of AAⅠ causing histopathological changes in the the above-mentioned tissues and organs of C3H/He mice was lower than that of C57BL/6 mice. Conclusion By analyzing the overall toxicity, serum biochemical indicators, causes of animal death, and histopathological changes caused by different doses of AAⅠ in C57BL/6 and C3H/He mice, it was concluded that C3H/He mice were more sensitive to acute toxicity of AA Ⅰ than C57BL/6 mice. This study not only verified the acute toxicity characteristics and target organs of AA Ⅰ on C57BL/6 and C3H/He mice, but also provided rich data support for comparing the sensitivity and tolerance of different strains of mice to AAⅠ acute toxicity, and provided detailed reference data for more scientific and reasonable research on AAⅠ in the future.

R965.3

国家自然科学基金资助项目（81503347）;药品监管科学全国重点实验室课题（2023SKLDRS0128）