目的 擬通過比較不同品系小鼠對(duì)馬兜鈴酸I（AAI）的耐受性及急性毒性反應(yīng)，以期為研究AAⅠ提供借鑒和指導(dǎo)。方法 采用ig給藥方式，單次給予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），每種品系小鼠均設(shè)置1個(gè)溶媒對(duì)照組，并于給藥后進(jìn)行一般癥狀觀察及體質(zhì)量測(cè)定。試驗(yàn)結(jié)束進(jìn)行剖檢、臟器稱質(zhì)量、血清生化指標(biāo)檢測(cè)及病理學(xué)檢查。結(jié)果 單次給予一定劑量AAⅠ可引起2種品系小鼠出現(xiàn)體質(zhì)量下降、消瘦、弓背及活動(dòng)減少，甚至死亡，并且C57BL/6小鼠出現(xiàn)上述改變的AAⅠ劑量低于C3H/He小鼠。C57BL/6小鼠的AAⅠ半數(shù)致死量（LD₅₀）為38.07 mg·kg^-1，C3H/He小鼠的AAⅠ LD₅₀為59.92 mg·kg^-1。C57BL/6小鼠AAⅠ最大耐受劑量（MTD）為17.1 mg·kg^-1，C3H/He小鼠的AAⅠ MTD為31.7 mg·kg^-1。給予一定劑量的AAI后，C57BL/6小鼠各項(xiàng)血清生化指標(biāo)未見改變，而C3H/He小鼠血清丙氨酸氨基轉(zhuǎn)移酶（ALT）、天冬氨酸氨基轉(zhuǎn)移酶（AST）、肌酐（CRE）水平升高。AAI可引起C57BL/6、C3H/He小鼠多個(gè)臟器出現(xiàn)急性損傷，如胸腺、脾臟、腎臟、肝臟及前胃，并且引起C3H/He小鼠上述組織器官出現(xiàn)組織病理學(xué)改變的AAⅠ劑量均低于C57BL/6小鼠。結(jié)論 通過對(duì)不同劑量AAⅠ所引起C57BL/6和C3H/He小鼠整體毒性、血清生化指標(biāo)、動(dòng)物死亡原因以及組織病理學(xué)改變分析，認(rèn)為C3H/He小鼠對(duì)AAⅠ的急性毒性比C57BL/6小鼠更加敏感。既驗(yàn)證了AAⅠ致C57BL/6和C3H/He小鼠的急性毒性特點(diǎn)和作用的靶器官，也為研究不同品系小鼠對(duì)AAⅠ急性毒性的敏感性和耐受性提供了數(shù)據(jù)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

國(guó)家自然科學(xué)基金資助項(xiàng)目（81503347）;藥品監(jiān)管科學(xué)全國(guó)重點(diǎn)實(shí)驗(yàn)室課題（2023SKLDRS0128）