地塞米松对大鼠生长板软骨细胞糖皮质激素受体的调节作用及抑制骨骼生长的机制研究

Dexamethasone up-regulates the expression of glucocorticoid receptor in growth plate and inhibits the longitudinal growth of bone:experiment with rats

目的观察药理剂量糖皮质激素对大鼠生长板软骨细胞糖皮质激素受体的调节作用;探究糖皮质激素抑制大鼠骨骼纵向生长的机制。方法 3周龄清洁级纯系雄性 SD 大鼠,实验组12只,地塞米松(200μg/100g,10d)处理;对照组8只,注射等容积的生理盐水。测量大鼠胫骨长。胫骨冠状面切片。Mallory 三色法染色观测生长板组织学,测量生长板总厚度、增殖带、肥大带厚度。糖皮质激素受体免疫组化分析。结果 (1)实验组大鼠胫骨长、生长板总厚度、增殖带、肥大带厚度分别为28.9mm±1.2mm,4.01μm±0.28μm,1.98μm±0.13μm,1.67μm±0.1μm;均明显落后于对照组30.5mm±1.1mm,5.53μm±0.46μm,2.25μm±0.30μm,2.87μm±0.19μm,差异均有统计学意义(均 P<0.05)。(2)生长板静止带和肥大带都表达糖皮质激素受体;而增殖带未见糖皮质激素受体表达。(3)地塞米松处理使生长板静止带和肥大带软骨细胞糖皮质激素受体表达增强。结论糖皮质激素受体是骨骼纵向生长所必需的。药理剂量糖皮质激素通过上调静止带和肥大带软骨细胞糖皮质激素受体抑制骨骼纵向生长。

Objective To investigate the regulation of the glucocorticoid of pharmacological doses on the expression of glucocorticoid receptor in growth plate and to explore the mechanism of the direct inhibition of the longitudinal growth of bone by dexamethasone. Methods Twenty 3-week-old male weanling SD rats were randomly divided into two groups： dexamethasone group （n = 12） , intraperitonally injected with dexamethasone 200 μg /100 g body weight once a day for 10 days and control group （n = 8） , intraperitonally injected with normal saline of the same volume. Ten days later the rats were killed. The length of the proximal tibia was excised, fixed and decalcified, and then paraffin embedded. Sections of 5 μm thick were cut and processed for histomorphometry The total height of growth plate, height of proliferative zone, and height of hypertrophic zone were determined. Results The length of tibia, total height of growth plate, height of proliferative zone, and height of hypertrophic zone of the dexamethasone group were28.9 mm±1.2 mm, 4.01 μm ±0.28 μm, 1.98 μm ±0. 13 μm, and 1.67 μm ±0. 18μm respectively, all significantly lower those of the control group （30.5 mm± 1.1 ram, 5.53 μm ± 0.46 μm, 2.25 μm ±0.30 μm, and 2.87 μm ±0.19 μm respectively, all P 〈0.01 ）. The resting chondrocytes and hypertrophic chondrocytes in the growth plates of the rats in the dexamethasone group all expressed glucocorticoid receptor, whereas the proliferating chondrocytes didn＇t. The absorbance values of the resting chondrocytes and hypertrophic chondrocytes in the growth plates of the dexamethasone group were 0. 238 ± 0. 026 and 0. 283 ± 0. 042 respectively, both significantly higher than those of the control group （0. 187 ± 0. 027 and 0. 211 ±0. 022 respectively, both P 〈 0.01 ）. Conclusion The glucocorticoid receptors are essential for the longitudinal growth of bone. The glucocorticoid of pharmacological dose inhibits the longitudinal growth of bone by up-regulating the expression of glucocorticoid receptor.