血管钙化大鼠模型肾脏β-Klotho及成纤维细胞生长因子受体1表达研究  

Expressions of Kidney β-Klotho and Fibroblast Growth Factor Receptor 1 in Experimental Rats Model With 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北京市心肺血管疾病研究所心内科28病房,北京市100029

出　　处：《中国循环杂志》2017年第5期507-510,共4页Chinese Circulation Journal

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)课题(2015CB554404);北京市自然科学基金项目(7142048)

摘　　要：目的:观察血管钙化对大鼠肾功能的损伤情况,及其与肾脏组织局部β-Klotho[成纤维细胞生长因子21(FGF21)的辅助因子]、成纤维细胞生长因子受体1(FGFR1)表达变化关系,探讨β-Klotho及FGFR1在血管钙化肾脏损伤中的作用和意义。方法:实验动物按电脑随机数字表法分为正常对照组和钙化组,每组6只。钙化组采用维生素D3联合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,以紫外-谷氨酸脱氢酶法检测大鼠血清尿素氮浓度,以生化法检测大鼠血钙及血磷浓度,以碱性磷酸酶(ALP)试剂盒检测大鼠肾脏组织ALP活性,以酶联免疫吸附法检测大鼠肾脏组织β-Klotho及FGFR1蛋白含量。结果:与正常对照组比较,血管钙化组大鼠血清肌酐及尿素氮水平升高[(35.200±4.087)μmol/L vs(26.000±5.0990)μmol/L,(P<0.05);(6.900±0.623)mmol/L vs(5.400±0.803)mmol/L,(P<0.05)];大鼠肾脏组织局部ALP活性升高[(60.510±31.090)U/g vs(26.590±8.664)U/g,(P<0.05)];肾脏组织β-Klotho蛋白表达量增加[(9.052±1.238)ng/mg vs(6.860±1.036)ng/mg,(P<0.05)],而血钙及血磷浓度及大鼠肾脏组织FGFR1蛋白含量较正常对照组未见明显变化。结论:大剂量维生素D3肌肉注射联合尼古丁灌胃可导致大鼠肾脏组织局部钙超载及微血管钙化形成,并导致肾功能不全,出现早期慢性肾脏病(CKD)临床表现。同时病变肾脏组织局部β-Klotho表达量上调,而FGFR1在肾脏组织局部未见明显变化,提示FGF21在血管钙化大鼠肾脏组织局部的调节作用可能不是通过增加其受体FGFR1的数量,而是通过上调其结合辅助因子β-Klotho的表达而实现的。同时提示β-Klotho参与了血管钙化肾脏损伤的早期调节过程,可能为预测机体钙超载情况及CKD早期的预警信号,对CKD的早期诊断具有一定价值。Objective： To observe the impact of vascular calcification on kidney injury rats with the expressions of β-Klotho, fibroblast growth factor receptor 1 （FGFR1） in kidney tissue in order to find the predictor for early chronic kidney disease （CKD）, to provide the prevention and investigation basis of vascular calcification and CKD. Methods： Vascular calcification model was induced by vitamin D3 and nicotine injection in experimental rats and the animals were divided into 2 groups： Normal control group and Calcification group, n=6 in each group. Serum levels of creatinine and urea nitrogen were examined by sarcosine oxidase method and UV-glutamate dehydrogenase method respectively; blood levels of calcium and phosphorus were detected by biochemistry method; kidney tissue alkaline phosphatases （ALP） activity was measured by ALP detection kit, protein expressions of β-Klotho and FGFR1 were assessed by ELISA. Results： Compared with Normal control group, Calcification group showed increased serum levels of creatinine （35.200±4.087） umol/L vs （26.000±5.0990） umol/L and urea nitrogen （6.900±0.623） mmol/L vs （5.400±0.803） mmol/ L, both P〈0.05; elevated kidney tissue ALP activity （60.510±31.090） U/g vs （26.590±8.664） U/g and β-Klotho protein expression （9.052±1.238） ng/mg vs （6.860±1.036） ng/mg, both P〈0.05. Blood levels of calcium, phosphorus and kidney tissue FGFR1 protein content were similar between 2 groups. Conclusion： Large dose vitamin D3 and nicotine injection may induce vascular calcification and early CKD symptom in experimental rats; β-Klotho protein expression was significantly increased suggesting that β-Klotho had been involved in the early regulation of vascular calcification and it could be used for the early diagnosis of CKD at certain point.

关 键 词：β-Klotho 受体 成纤维细胞生长因子 血管钙化 

分 类 号：R541[医药卫生—心血管疾病]