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目的 构建多黏菌素E诱导小鼠急性肾损伤（AKI）模型。方法 采用雄性C57BL/6小鼠，脱水后通过尾静脉或腹腔注射硫酸黏菌素构建模型，通过检测血清肌酐（Scr）值、尿素氮（BUN）值及肾组织中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、肾损伤分子-1(KIM-1)的mRNA表达水平，并结合HE染色和PAS染色评估肾组织病理损伤判定模型是否成功。结果 最终造模方法为脱水24 h后腹腔注射40 mg/（kg·d）(2次给药)的硫酸黏菌素1 d构建小鼠AKI模型。与对照组相比，硫酸黏菌素模型组的Scr及BUN水平分别升高至29.8倍和3.2倍，肾组织中NGAL与KIM-1 mRNA表达量显著升高（P<0.001）。组织病理学显示，硫酸黏菌素模型组肾小管上皮细胞坏死区域扩大，刷状缘结构完整性受损，空泡化病变密度增加，并伴有大量炎性细胞浸润，符合硫酸黏菌素致肾损伤的病理学改变。结论 本研究构建的多黏菌素E诱导小鼠AKI模型造模方法简单，Scr值升高显著与肾脏组织病理改变高度吻合，可为探索多黏菌素E致AKI发病机制和防治措施奠定基础。
Abstract：Objective To establish a murine model of acute kidney injury(AKI) induced by colistin. Methods Colistin sulfate was administered intravenously or intraperitoneally at escalating doses to dehydrated male C57 BL/6 mice for nephrotoxicity modeling. The serum creatinine, blood urea nitrogen, the mRNA expression levels of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in renal tissue were measured. Hematoxylin-eosin staining and periodic acid-Schiff staining were used to histopathologically validate the model. Results A mouse model of AKI was successfully established by administering a single intraperitoneal injection of colistin sulfate 40 mg/(kg·d)(twice administration) following a 24-hour dehydration period. Compared with the control group, the colistin sulfate-treated group exhibited 29.8-fold and 3.2-fold elevations in the serum creatinine and the blood urea nitrogen levels, respectively. Concurrently, the mRNA expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 was significantly upregulated in renal tissue(P < 0.001). Histopathological analysis demonstrated expanded areas of renal tubular epithelial cell necrosis, disrupted brush border integrity, increased vacuolization density, and prominent inflammatory cell infiltration in the colistin sulfate group, collectively aligning with the pathological hallmarks of drug-induced nephrotoxicity. Conclusion The colistin-induced murine AKI model established in this study employs a simple protocol, with significantly elevated Scr levels highly consistent with renal histopathological damage, which provides a foundation for determining the pathogenesis and therapeutic strategies of colistin-induced AKI.
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基本信息:
中图分类号:R692;R-332
引用信息:
[1]杨钦洁,刘昆,左笑丛,等.多黏菌素E诱导小鼠急性肾损伤模型的建立[J].中南药学,2026,24(02):11-16.
基金信息:
国家自然科学基金（No.82304636,No.U22A20386）; 湖南省自然科学基金（No.2023JJ40911,No.2023RC1032）
2025-05-14
2025
2026-01-15
2026
2
2026-02-20
2026-02-20