成纤维细胞生长因子23和骨形态发生蛋白7介导维生素D受体表达下降在2型糖尿病并发骨质疏松大鼠发病中的作用

Role of down-regulated expression of vitamin D receptor mediated by fibroblast growth factor 23 and bone morphogenetic protein 7 in rats with type 2 diabetes and osteoporosis

目的探讨2型糖尿病并发骨质疏松大鼠肾和骨组织维生素D受体（VDR）、成纤维细胞生长因子（FGF）23、骨形态发生蛋白（BMP）7的表达及意义。方法雌性Wistar大鼠随机分为假手术对照组（NS组）、单纯去卵巢组（NOVX组）、2型糖尿病假手术组（DS组）、2型糖尿病去卵巢组（DOVX组）。糖尿病组大鼠予高脂高糖饲料联合小剂量链脲佐菌素腹腔注射制备2型糖尿病模型，模型成功后去卵巢组行双侧卵巢切除术，去卵巢后4周、8周、12周末随机分批处死。用RT-PCR法观察各组。肾和骨组织VDR、FGF23、BMP7的mRNA表达，Western免疫印迹法观察各组肾组织VDR、FGF23、BMP7蛋白表达。结果成功制备2型糖尿病并发骨质疏松模型。随着时间延长，DS组和DOVX组肾和骨组织VDR、BMP7的mRNA表达和肾组织VDR、BMP7蛋白表达均较NS组和NOVX组降低，且以DOVX组表达最低（P〈0．05）；DS组和DOVX组骨组织FGF23的mRNA表达明显低于NS和NOVX组（0．566±0．059，0．452±0．057比1．008±0．068，0．520±0．049，P〈0．05），而DS组和DOVX组肾组织FGF23的mRNA和蛋白（1．034±0．071，1．136±0．112比0．919±0．086，0．952±0．143）表达明显高于NS和NOVX组，以DOVX组表达最高（P〈0．05）。结论FGF23和BMP7在肾和骨组织共同介导2型糖尿病并发骨质疏松大鼠维生素D受体表达中起不同作用。

Objective To investigate the expression and significance of Vitamin D receptor （VDR） , fibroblast growth factor（FGF） 23 and hone morphogenetic protein（BMP） 7 in the kidney and hone tissues in rats with type 2 diabetes and osteoporosis. Methods Female Wistar rats were randomly divided into four groups： sham control group （NS group）, ovariectomy group （NOVX group）, type 2 diabetes sham surgery group （DS group） and type 2 diabetic rats undergoing ovaIieetomy group （DOVX group）. In diabetes groups, rats were administrated with high- sugar- fat diet and intraperitoneal injection of small dose of streptozotocin so as to establish type 2 diabetes models （T2DMs）. After the models were successfully established, the ovariectomy groups received ovariectomy and were randomly sacrificed at the end of week 4, 8 and 12 after ovariectomy in batches. The mRNA expression levels of VDR, FGF23 and BMP7 in kidney and bone tissues in each group were observed by RT-PCR and the protein expression levels of VDR, FGF23 and BMP7 in kidney tissues by Western blot. Results The models of type 2 diabetes with osteoporosis were successfully established. Both mRNA expression levels of VDR and BMP7 in kidney and bone tissues and the protein expression levels of VDR and BMP7 in kidney tissues of DS and DOVX groups were lower than those of NS and NOVX groups along with time （P〈0.05）. DS and DOVX groups had significantly lower mRNA expression of FGF23 in bone tissues as compared with NS and NOVX groups（0.566±0.059,0.452±0.057 vs 1.008±0.068,0.520±0.049, P〈0.05）, but the mRNA and protein expression of FGF23 in kidney tissues of DS and DOVX groups was significantly higher than that of NS and NOVX groups （protein： 1.034±0.071, 1.136±0.112 vs 0.919±0.086, 0.952±0.143）, with expression level in DOVX group being the highest （P〈 0.05）. Conclusion The expression of vitamin D receptor（VDR） mediated by both FGF23 and BMP7 may not exert effects on rats of type 2 diabetes with osteoporosis.