糖皮质激素抑制Leptin、VEGF蛋白表达诱导骨质疏松作用机制研究

目的 通过比较糖皮质激素诱导骨质疏松模型大鼠（GIOP）在成模前后骨密度、病理组织以及瘦素（leptin）、血管内皮生长因子（vascular endothelial growth factor，VEGF）蛋白差异表达变化阐释糖皮质激素性骨质疏松的作用机制。方法 采取大腿内侧交替肌肉注射地塞米松注射液（DEX）建立骨质疏松症大鼠实验模型，连续注射8周，造模8周后处死各组大鼠，对右侧股骨胫骨进行骨密度检测、HE 染色，确定最佳造模剂量，继而通过免疫组织化学、蛋白免疫印迹的方法检测正常SHAM与DEX大鼠Leptin、VEGF蛋白的表达。结果 结合骨密度和HE染色的结果，确定DEX 2.5 mg/kg为地塞米松注射液诱导继发性骨质疏松的最佳造模剂量，免疫组织化学和蛋白免疫印迹检测发现，与SHAM组相比，DEX 2.5 mg/kg组大鼠Leptin、VEGF蛋白的表达均降低，差异有统计学意义(P＜0.05)。结论 糖皮质激素诱导的骨质疏松是通过抑制Leptin、VEGF蛋白表达，抑制血管生成进而抑制成骨发挥作用的，据此推测Leptin、VEGF可能是糖皮质激素性骨质疏松发病的潜在作用靶点。

Study on the mechanism of glucocorticoid-induced osteoporosis by inhibition of leptin and VEGF in rats

Objective To explore the mechanism of glucocorticoid-induced osteoporosis (GIOP) by comparing the changes of bone mineral density (BMD), pathological tissue, and the protein expression of leptin and vascular endothelial growth factor (VEGF) before and after modeling. Methods Rats received intramuscular injection of dexamethasone sodium phosphate (Dex) on their vastus for 8 weeks to establish the GIOP model. The rats were sacrificed after 8 weeks. Bone mineral density (BMD) and HE staining were performed on the right femur and tibia to determine the optimal modeling dose. The protein expressions of leptin and VEGF in rats of SHAM and DEX group were detected using immunohistochemistry and Western blotting. Results The results of BMD and HE staining showed that 2.5 mg/kg of Dex was the optimal dosage for GIOP modeling. The expression of leptin and VEGF in Dex2.5 mg/kg group decreased significantly (P<0.05) compared to those in Sham group, and the difference was statistically significant. Conclusion The effect of glucocorticoid on the induction of osteoporosis is through inhibition of leptin and VEGF expression, leading to the inhibition of angiogenesis and osteogenic differentiation. The present study indicates that leptin and VEGF might be potential targets for the pathogenesis of osteoporosis.