线粒体动力学蛋白异常表达参与阿德福韦酯致大鼠肾小管上皮细胞的损伤  

Effect of Abnormal Expression of Mitochondrial Dynamic Protein in Adefovir-induced Renal Tubular Epithelial Cell Injury in Rats

作　　者：朱燕[1] 王坚[2] ZHU Yan WANG jIan(Department of Nephrology Department of Pharmacy, Affiliated Second Hospital, Southeast University, Nan- ring 210003, China)

机构地区：[1]东南大学附属第二医院肾脏病科,南京210003 [2]东南大学附属第二医院药剂科,南京210003

出　　处：《药学与临床研究》2017年第5期373-376,共4页Pharmaceutical and Clinical Research

基　　金：南京市医学科技发展资金资助项目(YKK14151)

摘　　要：目的:探讨线粒体动力学相关蛋白drp1和mfn1对阿德福韦酯引起的大鼠肾小管上皮细胞损伤的机制。方法:根据阿德福韦酯给药剂量差异,对大鼠随机分为对照组和低、中、高剂量组;对照组给予生理盐水,其余3组分别给予0.2、0.4、0.8 mg·kg-1·d-1阿德福韦酯灌胃。给药60 d后取出大鼠肾脏,常规石蜡包埋,切片,HE染色观察肾小管上皮的形态学改变;免疫组化检测肾小管上皮中drp1和mfn1蛋白的表达。结果:阿德福韦酯干预的可见嗜酸性凝固坏死物和空泡样变性,近曲小管上皮细胞游离面的刷状缘结构不清,上皮细胞排列较紊乱。在drp1及mfn1的免疫组化中,高、中剂量组与对照组之间蛋白表达的平均光密度值差异有统计学意义(P<0.05)。结论:线粒体动力学蛋白drp1/mfn1可能介导了阿德福韦酯对人肾小管上皮细胞(HK-2)的损伤。Objective： To investigate the role of mitochondrial dynamics related proteins drp1 and mfn1 on adefovir dipivoxil-induced renal tubular epithelial cell injury in rat. Methods： The rats were randomly divided into groups given 0.2, 0.4 and 0.8 mg·kg-1·d-1 adefovir dipivoxil, respectively, and the control group given saline. The expressions of drp1 and mfn1 proteins in renal tubular epithelium were detected by immunohistochemistry. The morphological changes in renal tubular epithelium were observed by HE staining.Results： Adefovir dipivoxil intervention caused eosinophilic coagulation necrosis and vacuolar degeneration in the renal tubular lumen, unclear structure of free brush surface edge in the proximal tubule epithelial cells, and epithelial cells arranged in disorder. The average optical densities for drp1 and mfn1 protein expression in the high and middle adefovir dipivoxil dose groups were statistically different from that in the control group, respectively（P0.05）. Conclusion： Mitochondrial kinetic protein drp1/mfn1 may mediate adefovir-induced renal tubular epithelial cell injury.

关 键 词：线粒体动力学 阿德福韦酯 肾小管上皮细胞 

分 类 号：R965.1[医药卫生—药理学]