糖尿病肾病大鼠肾实质内小动脉钙化及其与骨基质蛋白的关系

目的：探讨糖尿病肾病（DN）大鼠肾内小动脉上核结合因子α亚单位1（Cbfa1）、骨钙素（OC）、骨保护素（OPG）的表达及其变化规律。方法：设对照组、糖尿病组两组,建立STZ诱导的DN大鼠模型。茜素红染色观察肾实质内小动脉周围钙盐沉积,并分别采用免疫组化及mRNA原位杂交法检测肾实质内小动脉上Cbfa1、OC、OPG的蛋白表达及基因定位。结果：（1）DN组肾内小动脉Cbfa1蛋白及mRNA表达明显高于对照组。（2）DN组第12周时出现OC mRNA弱表达,16周～24周出现OC蛋白弱表达,对照组无OC表达。（3）DN组OPG蛋白及mRNA在12周时达峰值,16周后下调,均明显高于对照组。结论：（1）DN大鼠肾内小动脉钙化前即已有Cbfa1、OC及OPG的表达。（2）Cbfa1是糖尿病血管钙化的重要转录因子,也是血管钙化的早期生物学标志。（3）OPG在DN时早期表达上调,后期表达下调。（4）肾内小动脉上Cbfa1、OC及OPG的表达变化可能参与DN进展。

Expression of Bone Matrix Protein in Renal Arteriole and its Potential Role in Diabetic Nephropathy Rats

Objective： We observed the expression of osteoprotegerin （OPG）, osteocalcin （OC） and core - binding factor α1 （Cbfal） in renal arteriole. Methods： Adult Sprague- Dawley male rats were divided into diabetic group and control group. Paraffin sections of renal tissue of rats at the same time points were stained by routine methods and immunohistochemistry, hybridization in situ. Results：（1） From 8- week, the number of Cbfal staining and mRNA in diabetic renal arteriole was significantly increased as compared with control group. （2） OC＇s protein and mRNA in diabetic renal was only detected at 16 and 24 weeks. （3） OPG- expressing in diabetic renal arteriole was found by immunohistochemistry and hybridization in situ from 4 - week to 24 - week with peak levels at 12 weeks, subsequently decreased after 12 week. Conclusion： （ 1 ） Bone matrix protein has already expressed in renal arteriole before the formation of vascular calcification. （2） Before vascular calcification, Cbfal in diabetic renal arteriole was significantly upregulated following OC＇s occurrence, which indicated that Cbfal was a key regulating factor of diabetic vascular calcification. （3） Early upregulation and late down- regulation of OPG is observed. （4） Alteration of the expression of Cbfal OC and OPG in renal arteriole may indicate that they participate in the development of DN.