非洛地平对DN大鼠肾内小动脉OPG表达的影响

Effect of felodipine on the expression of osteoprotegerin in renal arteriole of diabetic nephropathy rats

目的建立STZ诱导的DN大鼠模型，观察非洛地平对肾内小动脉上骨保护素（Osteoprotegerin，OPG）表达的干预作用。方法设对照组、DN组及非洛地平三组，茜素红染色观察肾内小动脉钙化程度。免疫组化、原位杂交检测OPG蛋白及基因表达。结果①DN组及非洛地平组第16-24周出现轻～中度钙化，对照组无钙化。②DN组及非洛地平组OPG蛋白及mRNA自8周表达开始增高，12周后开始下调，但均高于对照组，在16～24周时非洛地平组OPG表达强于DN组。结论①DN肾内小动脉发生钙化前即已有OPG的表达。②OPG早期表达上调可能为机体代偿性的保护机制所致，后期下调与促钙化因素的增强有关。③非洛地平干预后可上调OPG的表达。

Objective To establish the streptozotocin-induced diabetic nephropathy rat model and observe the expression of osteoprotegerin（OPG） in diabetic renal arteriole. Methods Adult Sprague-Dawley male rats were divided into diabetic group and felodipine therapy group, which were given a single intraperitoneal injection of streptozotocin, and control group. Felodipine group were received felodipine （10mg/kg. d by daily gastric garage） while other rats were received vehicle. The vascular calcification of renal arteriole was observed by alizarin red staining. Paraffin sections of renal tissue of rats were observed by routine methods and immunohistochemistry, hybridization in situ. The changes of OPG were quantificationally analyzed. Results From 16-weeks to 24-weeks , light to middle vascular calcification appeared in DN and felodipine group, while there was a weakly staining in control group. The number of OPG staining in DN group and felodipine group was significantly increased as compared with controls, being maximal at 12-weeks. From 16-weeks to 24-weeks, the expression of OPG in felodipine group was significantly upregulated compared with DN group. Conclusions OPG has already expressed in renal arteriole before the formation of vascular calcification. The early upregulation of OPG may be the compensative mechanism under pathological conditions and the late downregulation may relate to calcification factors. Felodipine can promote the expression of OPG in renal arteriole of diabetic rats.