摘要
目的探讨静脉注射基质金属蛋白酶抑制剂GM6001对激素性股骨头坏死(SINFH)大鼠组织形态学与基因表达的影响。方法 60只健康SD大鼠,经臀肌注射甲基泼尼松后制备激素性股骨头坏死模型,随机分为SINFH组、低剂量GM6001(GM6001-L)组和高剂量GM6001(GM6001-H)组,每组20只,GM6001-L组与GM6001-H组在造模同时经尾静脉注射50 mg/kg GM6001与100 mg/kg GM6001,1周1次,共计8周。另选取20只健康SD大鼠于臀肌注射等量生理盐水作为对照,经12周、20周后,观察SD大鼠股骨头形态学改变,以及过氧化氢酶体增殖物激活受体γ(PPAPγ)、11β-羟基类固醇脱氧酶(11β-HSD1)、Run相关转录因子2(Runx2)与CCAAT区/增强子结合蛋白α(C/EBPα)的变化。结果与对照组比较,造模组大鼠造模8周内的血清钙、磷水平降低;SINFH大鼠经GM6001治疗后8周内的血清钙、磷水平均显著升高,与SINFH组比较差异有统计学意义(P<0.05),且GM6001-H组血清钙、磷水平均高于GM6001-L组,差异有统计学意义(P<0.05);造模组大鼠造模8周内的BALP、Str ACP水平显著高于对照组,BGP、CT水平显著低于对照组,差异均有统计学意义(P<0.05);GM6001-L组与GM6001-H组经治疗后8周内的BALP、Str ACP水平均显著低于SINFH组,BGP、CT水平均显著高于SINFH组,差异均有统计学意义(P<0.05);造模组大鼠造模8周内的股骨转子、股骨头的骨密度及股骨头成骨细胞计数均低于对照组,破骨细胞数高于对照组,差异均有统计学意义(P<0.05);GM6001-L组与GM6001-H组经治疗后8周内的股骨转子、股骨头的骨密度及股骨头成骨细胞计数均高于SINFH组,破骨细胞计数低于SINFH组,差异均有统计学意义(P<0.05)。应用GM6001治疗后,与SINFH组比较,PPAPγ、11β-HSD1、C/EBPα表达减少,Runx2表达升高,且随剂量增加,PPAPγ、11β-HSD1、C/EBPα下降明显,而Runx2上升明显,与对照组比较,差异均有统计学意义(P<0.05)。结论大鼠股骨头坏死改变可能与激素抑制成骨及成脂分化基因表达有关,与11β-HSD1表达关系密切,而GM6001能改善这种病理改变以及基因异常表达,具有良好的临床应用价值。
Objective To investigate the effect of GM6001 on histomorphology and gene expression in rats with steroid-induced necroisis of femoral head（SINFH）. Methods A to tal of 60 healthy SD rats were intragluteally injected with methylprednisolone for the preparation model of avascular necrosis of femoral head, which were rand omly divided into the SINFH group, GM6001 low dose group（GM6001-L） and high dose group（GM6001-H） with 20 rats in each group. In GM6001-L group and GM6001-H group, the rats were intravenous injected with GM6001 by 50 mg/kg and 100 mg/kg respectively, 1 time per week, for 8 weeks. At the same time, 20 healthy SD rats injected with saline were taken as the blank control group. After 12 weeks and 20 weeks, the morphological changes of femoral head in SD rats, and the expression changes of peroxisome proliferator-activated receptor γ（PPARγ）, 11β-hydroxysteroid dehydrogenase type 1（11β-HSD1）, runt-related transcription factor-2（Runx2）, CCAAT/enhancer binding protein-α（C/EBPα）were observed. Results Compared with the control group, the serum calcium and phosphorus levels in the model group were decreased within 8 weeks. The levels of serum calcium and phosphorus in SINFH rats treated with GM6001 were significantly higher than those in SINFH group（P〈0.05）, and the levels in GM6001-H group were significantly higher than those in GM6001-L group（P〈0.05）. The levels of BALP and Str ACP in the model group were significantly higher than those in the control group within 8 weeks（P〈0.05）, while the levels of BGP and CT were significantly lower than those in the control group（P〈0.05）. The levels of BALP and Str ACP in GM6001-L group and GM6001-H group were significantly lower than those in SINFH group（P〈0.05）, while BGP, CT levels were significantly higher（P〈0.05）. Compared with the control group, the femur and femoral head bone density and femoral head bone cell counts in the model group rats within 8 weeks were significantly decreased, and the osteoclast significantly increased（P〈0.05）; Compared with the SINFH group, the femur and femoral head bone density and femoral head bone cell counts in GM6001-L and GM6001-H group rats after 8 weeks were significantly increased, and the osteoclast significantly decreased（P〈0.05）.With the increase dose of GM6001 treatment, compared with the SINFH group, the expression of PPARγ, 11β-HSD1, C/EBPα significantly decreased, while Runx2 significantly increased（P〈0.05）. Conclusion Necroisis of femoral head in rats may be closely related to the expression of hormone inhibiting osteogenic and adipogenic differentiation related gene and 11β-HSD1. GM6001 can improve the pathological changes and abnormal gene expression, which has the good clinical value.
出处
《海南医学》
CAS
2017年第15期2409-2413,共5页
Hainan Medical Journal
基金
河南省教育厅科学技术研究重点项目(编号:142182310068)
关键词
股骨头坏死
GM6001
组织形态学
基因表达
Avascular necrosis of the femoral head
GM6001
Histomorphology
Gene expression
