长期应用糖皮质激素对大鼠股骨头骨组织MMPs/TIMPs系统的影响

摘要

Objective To investigate the effects of long-term glucocorticoid medication on matrix metalloproteinase (MMPs)/tissue inhibitor of matrix metalloproteinases (TIMPs) system in bone tissues of rat femoral head, and to discuss the related action mechanism of glucocorticoid-induced necrosis of femoral head. Methods Forty healthy adult SD rats were randomly divided into 4 groups: high-dose glucocorticoid group (HD), medium-dose glucocorticoid group (MD), low-dose glucocorticoid group (LD) and control group, 10 rats in each. HD, MD and LD groups were differently treated with intramuscular injection of prednisolone (25, 12. 5, and 7 mg/kg body weight) twice a week, respectively; the control group was only treated with the same volume of sodium chloride. After 4 weeks' intervention, osteonecrosis of left femoral heads was detected by HE staining; the total RNA of right femoral head bone tissues total RNA was extracted; and the expression levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNAs were examined by real-time quantitative polymerase chain reaction. Results The early-stage necrosis rate of femoral head was 83.33% (5/6), 66.67% (6/9), 30% (3/10) and 0 (0/10) in HD, MD, LD and control groups, respectively. MMP-2 and MMP-9 mRNA expression levels in HD, MD and LD groups were higher than those in control group and were positively correlated with the hormone dosage. HD and MD groups differed from control group significantly (P＜0.05). TIMP-1 and TIMP-2 mRNA expression levels were significantly lower in HD, MD and LD groups than in control group, and were negatively correlated with the hormone dosage (P＜0.05). Conlusion Glucocorticoid-induced necrosis of femoral head may be related to glucocorticoid's regulation of the expression levels of MMPs/TIMPs mRNAs.%目的 观察长期应用糖皮质激素对大鼠股骨头骨组织中基质金属蛋白酶(MMPs)/基质金属蛋白酶组织抑制剂(TIMPs)系统的影响,探讨长期应用糖皮质激素导致股骨头坏死的相关机制.方法 健康SD大鼠40只,雌雄各半,随机分为低、中、高剂量激素组和对照组,每组10只.低、中、高剂量组动物分别给予肌肉注射醋酸泼尼松龙7、12.5、25 mg/kg体重,每周2次；对照组给予相同体积生理盐水肌注.4周后取左侧股骨头骨组织石蜡包埋,HE染色,鉴定股骨头坏死情况；取右侧股骨头骨组织提取总RNA,采用实时定量聚合酶链反应(RT-PCR)技术检测MMP-2、MMP-9、TIMP-1、TIMP-2 mRNA表达水平.结果 高、中、低剂量激素组和对照组动物初期股骨头坏死发生率分别为83.33％(5/6)、66.67％ (6/9)、30℃(3/10)、0(0/10);各激素组与对照组比较,MMP-2、MMP-9 mRNA表达增高,与激素用量呈正相关,其中,中、高剂量激素组与对照组比较,差异有统计学意义(P＜0.05)；TIMP-1、TIMP-2 mRNA表达水平降低,且与激素用量呈负相关,差异有统计学意义(P＜0.05).结论 长期应用糖皮质激素致股骨头坏死的效应可能与其调控MMPs/TIMPs系统表达有关.