血管钙化大鼠肾脏损伤及其FGF21的表达  

Study on the kidney impairment and expressions of FGF21 from a rat model of vascular calcification

作　　者：史雨晨[1] 柳景华[1] 

机构地区：[1]首都医科大学附属北京安贞医院心内科北京市心肺血管疾病研究所,100029

出　　处：《中华医学杂志》2016年第46期3741-3744,共4页National Medical Journal of China

基　　金：国家自然科学基金（81570388）;国家重点基础研究发展计划（973计划）（2015CB554404）;北京市自然科学基金（7142048）

摘　　要：目的观察血管钙化模型大鼠肾功能损伤及其病理变化，以及与肾脏组织局部成纤维细胞生长因子21（FGF21）表达变化关系，探讨FGF21在血管钙化肾脏损伤中的作用和意义。方法14只8周龄雄性SD大鼠，适应环境饲养7 d后按计算机随机数字法分为对照组和维生素D3＋尼古丁（VDN）组，每组7只，VDN组采用维生素D3和尼古丁诱导大鼠血管钙化模型。以肌氨酸氧化酶法检测大鼠血清肌酐浓度，以碱性磷酸酶（ALP）试剂盒检测大鼠肾脏组织ALP活性，以放射免疫法检测大鼠肾脏组织FGF21蛋白含量，以苏木精-伊红（HE）染色观察肾脏组织结构变化。结果VDN组大鼠血清肌酐浓度较对照组升高[（34.00±4.69）比（27.17±5.38）μmol/L，P〈0.05]，且HE染色可见钙化组大鼠肾脏病理性改变；VDN组大鼠肾脏组织局部ALP活性高于对照组[（62.59±22.62）比（29.89±11.78）U/g，P〈0.05]；与对照组相比，VDN组肾脏组织FGF21蛋白表达量较对照组增加[（0.583±0.340）比（0.207±0.105）ng/mg，P〈0.05]，同时肾脏组织FGF21蛋白含量与ALP水平呈正相关（r＝0.878，P〈0.05）。结论大剂量维生素D3和尼古丁联合应用可造成大鼠肾脏组织局部钙超载及微血管钙化形成，并导致肾功能损伤及病理改变；同时病变肾脏组织局部FGF21表达量上调，并与钙化水平具有一定相关性，FGF21可能参与了血管钙化及肾脏损伤的发生发展过程。Objective To investigate the injury and pathological changes of kidney in a rat model of aortic vascular calcification and to explore the expressions of fibroblast growth factor 21 （FGF21）.Methods A total of 14 Spraugue Dawley （SD） rats were randomly divided into two groups： control group and vitamin D3＋ nicotine （VDN） group, with 7 rats in each group.The rats in VDN group received vitamin D3 and nicotine to induce vascular calcification.The content of serum creatinine was determined by sarcosine oxidase method.Alkaline phosphatases （ALP） activity was detected by ALP detection kit.The protein levels of FGF21 were measured by radioimmunoassay （RIA）. The structure of kidney was observed by hematoxylin and eosin staining.Results The serum concentration of creatinine in VDN group was significantly higher than control group[（34.00±4.69） vs （27.17±5.38） μmol/L, P〈0.05], and the renal pathological changes in VDN group were more apparent. ALP activity in VDN group was significantly higher than that in control group[（62.59±22.62） vs （29.89±11.78） U/g, P〈0.05]. Expression of FGF21 in VDN group increased obviously, compared with that in control group[（0.583±0.340） vs （0.207±0.105） ng/mg, P〈0.05]. Meanwhile, the elevated levels of FGF21 were positively correlated with up-regulation of ALP in calcified kidneys （r=0.878, P〈0.05）.Conclusions Flushing dose of vitamin D3 and nicotine can induce the change of pathology and function of the kidney.Meanwhile, the expression of FGF21 in kidney up-regulated significantly, suggesting that FGF21 may be involved in the occurrence and development of vascular calcification and subsequent kidney injury.

关 键 词：成纤维细胞生长因子21 血管钙化 肾脏损伤 大鼠 

分 类 号：R692[医药卫生—泌尿科学]