糖皮质激素对大鼠骨折愈合方式的影响

Effects of glucocorticoids on fracture healing in rats

目的:探讨糖皮质激素对大鼠骨干骨折愈合方式的影响。方法:取3月龄雌性SD大鼠60只分为实验组和对照组,实验组肌肉注射醋酸强的松5mg·kg-1.d-1,对照组注射等容积的生理盐水。3周后制成胫骨干骨折模型,骨折后不同阶段处死,分别进行组织学、骨密度、Western印迹检测骨痂中Ⅱ型胶原蛋白的表达以及生物力学测定。结果:肌肉注射醋酸强的松3周后骨密度检查证实模型制造成功。骨折后第3d2组均开始形成原始骨痂;第2周实验组软骨骨痂明显比对照组少,第4-6周实验组骨痂面积高于对照组,且软骨骨痂比例较高,骨密度减低。实验组中Ⅱ型胶原蛋白表达明显延迟。第6周生物力学测定对照组实际最大载荷为(69.77±8.46)N,较实验组(51.38±3.37)N增加35.8%。结论:大剂量糖皮质激素在大鼠骨折早期延缓软骨骨痂的产生,在骨折中后期使软骨性骨痂至骨性骨痂演变过程减缓。Ⅱ型胶原蛋白的表达延迟可能是其对骨折愈合产生不利影响的原因之一。

AIM： To explore the effects of glucocorticoids on fracture healing in a rat model of tibial fracture. METHODS： Sixty three months old female SD rats were divided into control and glucocorticoid-treated group. A glucocorticoid-induced osteoporosis model was established by intramuscular injection of prednisolone acetate （5 mg·kg-1·d-1 for 3 weeks）, in which the tibial was osteotomized by a wire saw as fracture healing model and internal fixed with a Kirschner pin. The rats were scarified at different time points after operation. The callus formation was monitored over a period of 6 weeks by histological method, bone mineral density （BMD） detection and biomechanical examination. Western blotting was used to measure the expression of type II collagen. RESULTS： A glucocorticoid-induced osteoporosis model was successfully established and conformed by BMD measurement. The formation of primary callus was observed in both groups 3 days after fracture. At 2 weeks after injury, the glucocorticoid-treated group had a lower BMD and less cartilage matrix as compared to control group. An increase in bone callus and chondrogenesis was observed at 4 to 6 weeks after fracture in glucocorticoid-treated group as compared to control group. The expression of type II collagen was delayed in glucocorticoid-treated group. Biomechanical measurement showed that the actual maximum load was increased by 35.8% in control group as compared to glucocorticoid-treated group at 6th week. CONCLUSION： These results indicate that chondrogenesis and transformation from cartilage callus to bony callus are delayed by glucocorticoids. The retardation of collagen Ⅱ production may be the reason for the inhibition of fracture healing.