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中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (11): 1508-1515.doi: 10.12092/j.issn.1009-2501.2025.11.007

• 基础研究 • 上一篇    下一篇

肾小管上皮细胞特异性FXR敲除小鼠模型建立及功能初探

刘兆丰1，李玲1，那淑芳1，乐江2，叶啟发1，3   

  1. 1武汉大学中南医院，武汉大学肝胆疾病研究院，武汉大学移植医学中心，国家人体捐献器官获取质量控制中心，移植医学技术湖北省重点实验室，武汉  430071，湖北；2武汉大学基础医学院药理教研室，武汉  430071，湖北；3中南大学湘雅三医院，国家卫生健康委移植医学转化研究重点实验室，长沙  410013，湖南

  • 收稿日期:2025-01-02 修回日期:2025-01-17 出版日期:2025-11-26 发布日期:2025-12-04
  • 通讯作者: 叶啟发，男，教授，主任医师，研究方向：肝胆外科，器官移植。 E-mail： yqf_china@163.com
  • 作者简介:刘兆丰，女，硕士，研究方向：肝胆外科与器官移植。 E-mail： brittany11277@163.com
  • 基金资助:
    国家自然科学基金青年基金（82404775）；中央高校基本科研业务费专项资金青年教师资助项目（2042023kf0064）；武汉大学中南医院2024年科技创新培育基金（CXPY2024025）；2023年武汉大学中南医院转化医学及交叉学科研究联合基金（ZNJC202319）

Establishment and function of a mouse model of renal tubular epithelial cell-specific FXR gene knockout 

LIU Zhaofeng1, LI Ling1, NA Shufang1, YUE Jiang2, YE Qifa1,3   

  1. 1Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan 430071, Hubei, China; 2Department of Pharmacology,?School?of?Basic Medical?Sciences,?Wuhan University, Wuhan 430071, Hubei, China; 3The 3rd Xiangya Hospital of Central South University, NHC key laboratory of translational research on transplantation medicine, Changsha 410013, Hunan, China
  • Received:2025-01-02 Revised:2025-01-17 Online:2025-11-26 Published:2025-12-04

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摘要：

目的：探讨肾小管上皮细胞特异性法尼酯X受体（FXR）基因敲除对小鼠肾功能的影响。方法：基于cre-loxp系统构建肾小管上皮细胞特异性FXR基因敲除小鼠。采用qRT-PCR检测肾脏FXR的mRNA水平，Western blot和免疫荧光法检测肾脏FXR的蛋白表达，苏木精-伊红染色、过碘酸雪夫染色观察小鼠肾脏形态，透射电子显微镜观察超微结构下肾小管形态。试剂盒检测血清肌酐（Scr）、尿素氮（BUN）和尿β-N-乙酰氨基葡萄糖苷酶（β-N-acetyl glucosaminidase，NAG）水平评估肾功能。结果：肾小管上皮细胞特异性FXR敲除小鼠肾脏FXR的mRNA水平、蛋白表达水平降低，肾小管可见空泡化，血清中SCr、BUN水平未见明显改变，但尿液中NAG水平显著升高。结论：肾小管上皮细胞特异性FXR基因敲除小鼠模型建立成功，FXR敲除导致肾小管上皮细胞空泡化和肾功能降低。

关键词: cre-loxp系统, 法尼酯X受体, 肾小管上皮, 空泡化, 肾功能

Abstract:

AIM: To investigate the effect of FXR gene knockout on the kidney of mice. METHODS: Renal tubular epithelial cell-specific FXR gene knockout mice were constructed based on the cre-loxp system. qRT-PCR was used to detect the mRNA transcription level of FXR in kidney, western blot and immunofluorescence were used to detect the expression of FXR protein in kidney, hematoxylin-eosin staining and periodate sherff staining were used to observe the kidney morphology of mice, and transmission electron microscopy was used to observe the tubule morphology under ultrastructure. Renal function was assessed by testing Scr, BUN, and urine NAG. RESULTS: The mRNA transcription level and protein expression level of FXR in the renal tubular epithelial cells were decreased after specific knockout of FXR in mice, and there were obvious vacuolization in the renal tubules. The levels of SCr and BUN in the serum were not significantly changed, but the level of NAG in urine was increased. CONCLUSION: The mouse model of FXR gene knockout in renal tubular epithelial cells has been successfully established, and FXR knockout leads to vacuolization of renal tubular epithelial cells and impairment of renal function.

Key words: cre-loxp system, farnesoid X receptor, renal tubular epithelium, vacuolation, kidney function

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