摘要
目的探讨缺血性急性肾损伤(IAKI)大鼠miR-214介导的缺氧诱导因子l(HIFlα)、肾损伤分子1(KIMl)信号通路作用机制。方法将48只大鼠分为假手术组、IAKI组和miR-214组,建立IAKI组和miR-214组IAKI大鼠模型,48 h后抽取3组大鼠眼眶静脉血并收集尿液,检测生化指标及KIM1表达,采用Masson’s Trichrome、TUNEL、免疫印迹及PCR检测肾组织病理、肾小管细胞凋亡及肾组织中HIF1α、KIM1蛋白及mRNA表达。结果IAKI组大鼠血清中血清肌酸酐(Scr)、血尿素氮(BUN)和尿24 h三磷酸尿苷(UTP)表达高于假手术组(P<0.05),miR-214组大鼠血清中Scr、BUN、24 h UTP含量高于IAKI组(P<0.05);假手术组肾脏组织结构完整,肾小管和肾小球形态良好;IAKI组肾小球间质增多,肾间质增宽,炎症浸润严重,肾小管严重萎缩;miR-214组与IAKI组相比,肾小球硬度增加,肾小管周围组织炎症浸润更加严重。IAKI组大鼠肾小管细胞凋亡最为严重,凋亡程度明显高于假手术组;miR-214组与IAKI组相比肾小管细胞凋亡程度增加;IAKI组大鼠肾组织中HIF1α、KIM1蛋白以及mRNA表达高于假手术组(P<0.05),miR-214组与IAKI组相比肾组织HIF1α、KIM1蛋白及mRNA表达升高(P<0.05)。结论miR-214升高会加快肾小管细胞凋亡,加重肾组织损伤,增加HIF1α、KIM1表达,进一步加重IAKI大鼠病情。
Objective To investigate the mechanism of mir-214-mediated hypoxia-inducible factor alpha(HIF1 alpha)and kidney injury molecule-1(KIM1)signaling pathways in rats with ischemic acute kidney injury.Methods Rats were divided into three groups,with 16 rats in each group sham operation group,IAKI group and miR-214 group.The model rats in IAKI group and miR-214 group were treated with ischemic acute kidney injury.Orbital venous blood was extracted from all rates,and urine was collected to determine biochemical parameters and KIM1 expression.Masson's Trichrome,TUNEL,immunoblotting and PCR were used to detect renal histopathology,apoptosis of glomerular epithelial cells and expression of HIF1α,KIM1 protein and mRNA in renal tissues.ResultsThe Scr,BUN and 24 h UTP levels of rats in the IAKI group were higher than the sham group(P<0.05),while the levels of MIR-214 group were higher than the IAKI group.The sham operation group revealed intact renal tissue structure and good renal tubular and glomeruli.The IAKI group displayed increased glomerular interstitial,widening renal interstitial and inflammation.Compared with IAKI group,miR-214 group showed more renal interstitial inflammation,more serious hardness increased and tubular atrophy.The apoptosis of IAKI group was more severe than sham group,while the miR-214 group was more severe than the IAKI group.The levels of HIF1αand KIM1 proteins and mRNA in the IAKI group were higher than those in the sgam group(P<0.05),and the levels of the miR-214 group were higher than IAKI group(P<0.05).Conclusion The increase of miR-214 accelerates the apoptosis of glomerular epithelial cells,impaires renal tissue damage,and mediates the elevation of HIF1αand KIM1,further aggravates the condition of IAKI rats.
作者
李丹
安娜
柳璐
徐岩
LI Dan;AN Na;LIU Lu;XU Yan(Department of Nephrology, Qingdao Central Hospital Qingdao 266000,China;Department of emergency,Qing dao Central Hospital Qingdao 266000,China;Department of Nephrology, Affiliated Hospital of Qingdao University Qingdao266000,China)
出处
《海南医学院学报》
CAS
2019年第24期1847-1851,共5页
Journal of Hainan Medical University
基金
国家自然科学基金项目(81770679)~~
