香叶醇对耐药大肠埃希菌感染小鼠肾损伤的保护机制OA北大核心
Protective mechanism of geraniol on kidney injury caused by multidrug-resistant Escherichia coli in mice
为探讨香叶醇对多重耐药大肠埃希菌感染小鼠肾脏损伤的保护作用及其潜在机制,假设香叶醇通过调节抗氧化和抗炎信号通路减轻肾脏病理损伤.采用多重耐药大肠埃希菌腹腔注射制备小鼠感染模型,用香叶醇(0.092 g/kg)肌内注射进行治疗,每天给药1次,连续3 d,第4 d收集肾脏标本.苏木精-伊红染色法观察肾脏病理学变化,qPCR检测肾脏Nrf2、HO-1、GPX4的mRNA表达,试剂盒法测定肾脏LDH和SOD的含量,采用免疫组化法和Western Bolt检测Nrf2、HO-1、GPX4的蛋白表达情况.多重耐药大肠埃希菌感染后,小鼠肾脏组织出现髓质淤血、集合管扩张、多灶性淤血并伴有明显的炎细胞浸润等病理损伤改变,香叶醇治疗组肾脏炎性细胞浸润现象有所减轻,缓解肾小球和肾小管淤血病理损伤,LDH活力降低,SOD活性增高(P<0.05).香叶醇显著上调肾脏Nrf2、HO-1、GPX4的mRNA表达(P<0.05),且显著提高Nrf2、GPX4蛋白表达(P<0.05),HO-1表达无显著变化.香叶醇具有缓解多重耐药大肠埃希菌引起的肾脏损伤的作用,作用机制与其激活Nrf2/HO-1/GPX4信号通路,缓解炎症氧化应激损伤等有关,提示香叶醇具有控制多重耐药大肠埃希菌感染药物的开发与应用前景.
To investigate the protective effect and underlying mechanisms of geraniol against kidney injury in-duced by multidrug-resistant Escherichia coli in mice,we hypothesizing that geraniol alleviates renal patho-logical damage by modulating antioxidant and anti-inflammatory signaling pathways.Multidrug-resistant Esch-erichia coli bacterial suspension was intraperitoneally injected into mice,the mouse bacterial infection model was established followed by intramuscular injection of 0.092 g/kg geraniol once daily for three consecutive days,and mouse kidneys were collected on the 4th day.Histopathological changes in renal histology after in-fection were observed by the H&E staining method.The relative mRNA expression levels of Nrf2,HO-1 and GPX4 in the kidney were measured by qPCR,and the contents of LDH and SOD in the kidney were de-tected by assay kits.Immunohistochemistry and Western blot were used to detect the protein expressions of Nrf2,HO-1,and GPX4.Multidrug-resistant E.coli infection led to medullary congestion,dilated collecting ducts,multifocal congestion,and significant inflammatory cell infiltration in kidneys.In the geraniol-treated group,inflammatory cell infiltration was reduced,and pathological damage to the glomeruli and renal tubules was alleviated.Additionally,LDH activity was significant decreased,while SOD activity was increased(P<0.05).Geraniol significantly upregulated the mRNA expression of Nrf2,HO-1 and GPX4(P<0.05)and enhanced the protein expression of Nrf2 and GPX4(P<0.05),though HO-1 protein expression remained unchanged.These findings suggest that geraniol effectively mitigates kidney injury caused by multidrug-resistant E.coli,potentially through activation of the Nrf2/HO-1/GPX4 signaling pathway,which alleviates inflammatory and oxidative stress damage.This highlights its potential for the development of drugs targeting multidrug-resistant E.coli infections.
王雨珍;宁溢潇;代敏
成都医学院检验医学院,成都 610500||成都医学院 四川省动物源性食品兽药残留防控技术工程实验室,成都 610500成都医学院检验医学院,成都 610500||成都医学院 四川省动物源性食品兽药残留防控技术工程实验室,成都 610500成都医学院检验医学院,成都 610500||成都医学院 四川省动物源性食品兽药残留防控技术工程实验室,成都 610500
药学
多重耐药香叶醇大肠埃希菌Nrf2/HO-1/GPX4信号通路肾损伤
Multidrug resistanceGeraniolEscherichia coliNrf2/HO-1/GPX4 signaling pathwayKidney damage
《四川大学学报(自然科学版)》 2025 (3)
713-720,8
四川省科技厅重点研发计划(2024YFFK0090)四川省中医药管理局创新团队项目(2023ZD02)国家自然科学基金项目(82472328).
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