1 驻马店魏道德骨科医院康复科，河南 驻马店 463000
2 驻马店魏道德骨科医院风湿免疫科，河南 驻马店 463000
3 驻马店魏道德骨科医院疼痛科，河南 驻马店 463000
4 河南省中医院风湿免疫科，河南 郑州 450002
目的：探究通血健骨丸对兔缺血性坏死股骨头中低氧诱导因子1α(hypoxia inducible factor 1α，HIF-1α)，血管内皮生长因子(vascular endothelial growth factor，VEGF)和骨形态发生蛋白2(bone morphogenetic protein，BMP-2)表达的影响。方法：臀肌注射醋酸泼尼松龙诱导兔缺血性股骨头坏死模型，正常对照组不做任何处理，造模后，观察正常对照组和模型组一般生理状况，肉眼和X射线检查其股骨头的形态，HE染色检查病理学变化；将构建的模型分成4组，命名为模型组、通血健骨丸低剂量组、通血健骨丸中剂量组和通血健骨丸高剂量组，通血健骨丸组按照低、中、高剂量分别给予300，400，500 mg/kg的通血健骨丸，正常对照组和模型组给予等量容积生理盐水，灌胃治疗；应用实时荧光定量PCR(qRT-PCR)和Western印迹检测HIF-1α，VEGF和BMP-2表达情况。结果：建模后，模型组食量减少，精神萎靡，活动范围局限；模型组股骨头表面凹陷、骨密度不均一、负重区囊性变、关节间隙狭窄，软骨下脂肪细胞增大、骨小梁变细、骨细胞萎缩；模型组HIF-1α，VEGF和BMP-2的表达量显著低于正常对照组(P<0.05)；通血健骨丸组HIF-1α，VEGF和BMP-2的表达量显著高于模型组(P<0.05)；且随着通血健骨丸剂量增加，HIF-1α，VEGF和BMP-2的表达量显著提高(P<0.05)，呈剂量依赖性。结论：通血健骨丸能够促进兔缺血性坏死股骨头中HIF-1α，VEGF和BMP-2上调表达，进而促进骨骼修复。关键词： 通血健骨丸；缺血性股骨头坏死；低氧诱导因子1α；血管内皮生长因子；骨形态发生蛋白2
Effect of blood invigorating bone pill on HIF-1α, VEGF and BMP-2 expression of rabbits with avascular necrosis of femoral head
Foundation: This work was supported by the Henan Medical Science and Technology Research Project, China (201504152).
Objective: To explore the influence of blood invigorating bone pill on hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP-2) expression of rabbits with avascular necrosis of femoral head. Methods: The model of rabbit with avascular necrosis of femoral head was induced with prednisolone acetate by gluteal injection, and the normal control group were not given any treatment. After modeling, general physiological condition of normal control group and model group were observed, and the morphology of femoral head was examined by using naked eye and X-ray. The model were divided into four groups, and named for model group, blood invigorating bone pill low dose group, blood invigorating bone pill medium-dose group, and blood invigorating bone pill high dose group, with 300, 400, 500 mg/kg, respectively. The normal control group and model group were given the same volume of normal saline, and gastric lavage treatment. HIF-1α, VEGF and BMP-2 expression was detected by using real time quantitative PCR (qRT-PCR) and Western blot. Results: After modeling, there was less appetite, less mental activity, and limited range of activities in the model group. In the model group, the surface of femoral head was depressed, the bone density was uneven, the weight-bearing area was cystic, the joint space was narrow, the subchondral fat cells increased, the trabecular bone became thin and the bone cells atrophied. HIF-1α, VEGF and BMP-2 expression in the model group were significantly lower than those in the normal control group (P<0.05). HIF-1α, VEGF and BMP-2 expression in the blood strengthening bone pill group were significantly higher than those in the model group (P<0.05), HIF-1α, VEGF and BMP-2 increased significantly with with the increase in the amount of blood strengthening bone pill (P<0.05), showing dose-dependent. Conclusion: Blood invigorating bone pill can promote HIF-1α, VEGF and BMP-2 up-regulation expression of rabbits with avascular necrosis of the femoral head, and then promote bone repair.Keywords： blood invigorating bone pill; avascular necrosis of femoral head; hypoxia inducible factor 1α; vascular endothelial growth factor; bone morphogenetic protein 2