微泡增强超声抑制激素性股骨头坏死的动物实验研究

发布时间：2018-08-14 09:23

【摘要】：背景:激素性股骨头坏死是非创伤性股骨头坏死中最常见的病因之一,目前尚没有有效的手段来预防和治疗激素性股骨头坏死。已经有动物体内实验研究证明低强度脉冲超声可在一定程度上抑制激素性股骨头坏死的进展。我们在超声干预的过程中加入微泡来验证微泡联合低强度脉冲超声是否可提高单纯超声干预对激素性股骨头坏死的抑制作用。方法:兔子激素性股骨头坏死的模型是通过一次低剂量内毒素联合多次大剂量甲强龙注射来建立的。24只雄性新西兰兔子(随机平均分为三组,对照组(造模后不作治疗),超声组(造模后低强度脉冲超声治疗)和微泡超声组(造模后微泡局部注射联合低强度脉冲超声治疗)。低强度脉冲超声的强度为200mW/cm2,每天治疗20分钟,共治疗6周。6周后获取双侧股骨头标本行micro-CT,生物力学,实时定量PCR,western blot,组织学和免疫组织化学等检测。结果:经过6周的干预后,对照组中,骨密度,骨小梁数量,抗压载荷和骨矿化率等显著降低,表明我们的选模是成功的。微泡组中,骨密度值较超声组显著增高(932.6 ± 6.861 mg/cm2 vs.894.5 ± 12.84 mg/cm2),具有统计学差异(p0.001)。微泡组中,骨小梁数量较超声组显著增多(2.352 ± 0.06980/mm vs.2.213 ±0.07245/mm),具有统计学差异(p0.001)。骨小梁厚度在微泡组中较超声组有所增厚,但无统计学差异(p=0.286)。微泡组中,骨矿化率显著高于超声组(2.660±0.2390μm/dayvs.1.913 ± 0.1457μm/day),具有统计学差异(p=0.008)。微泡组最大抗压载荷值显著高于超声组(467.2 ± 65.96N vs.365.6 ±57.40N),且差异有统计学意义(P0.001)微泡超声显著增强了 FHN骨组织中VEGF和BMP-2的表达。微泡组血管数量明显多于超声组(13.7±4.3/mm2vs.8.3±1.6/mm2),差异有统计学意义(p=0.041)。微泡组的血管最小直径大于超声组(28.6 ± 4.6μm vs.23.9 ± 4.2μm),但是差异没有统计学意义(p=0.205)。结论:我们的研究结果证实,相比单纯使用低强度脉冲超声,微泡超声对激素性股骨头坏死进展的抑制作用更强。
[Abstract]:Background: hormonal necrosis of the femoral head is one of the most common causes of nontraumatic osteonecrosis of the femoral head. In vivo experiments have shown that low-intensity pulsed ultrasound can inhibit the progress of hormone-induced femoral head necrosis to some extent. We added microbubbles in the process of ultrasound intervention to verify whether microbubbles combined with low-intensity pulsed ultrasound could increase the inhibitory effect of ultrasound alone on steroid-induced femoral head necrosis. Methods: the model of steroid-induced femoral head necrosis in rabbits was established by a low dose endotoxin injection combined with a large dose of methylenolone injection. 24 male New Zealand rabbits were randomly divided into three groups. Control group (no treatment after modeling), ultrasound group (low intensity pulsed ultrasound treatment after model making) and microbubble ultrasound group (local injection of microbubble combined with low intensity pulsed ultrasound treatment). The intensity of low-intensity pulsed ultrasound was 200mW / cm ~ 2. After 6 weeks of treatment, micro-CTS, biomechanics, real-time quantitative PCRX Western blot, histology and immunohistochemistry were performed. Results: after 6 weeks of intervention, bone mineral density, bone trabecula number, compressive load and bone mineralization rate were significantly decreased in the control group, indicating that our model selection was successful. The BMD in the microbubble group was significantly higher than that in the ultrasound group (932.6 卤6.861 mg/cm2 vs.894.5 卤12.84 mg/cm2). The number of bone trabeculae in microbubble group was significantly higher than that in ultrasound group (2.352 卤0.06980/mm vs.2.213 卤0.07245/mm). The thickness of trabecular bone in microbubble group was thicker than that in ultrasound group, but there was no statistical difference (p0. 286). The bone mineralization rate in the microbubble group was significantly higher than that in the ultrasound group (2.660 卤0.2390 渭 m/dayvs.1.913 卤0.1457 渭 m/day). The maximum compressive load in the microbubble group was significantly higher than that in the ultrasound group (467.2 卤65.96N vs.365.6 卤57.40N), and the difference was statistically significant (P0.001). The expression of VEGF and BMP-2 in the bone tissue of FHN was significantly enhanced by microbubble ultrasound. The number of blood vessels in the microbubble group was significantly higher than that in the ultrasound group (13. 7 卤4.3/mm2vs.8.3 卤1.6/mm2), and the difference was statistically significant (p0. 041). The minimum diameter of blood vessel in the microbubble group was larger than that in the ultrasound group (28.6 卤4.6 渭 m vs.23.9 卤4.2 渭 m), but the difference was not statistically significant (p0. 205). Conclusion: our results confirm that microbubble ultrasound can inhibit the progression of steroid-induced osteonecrosis of femoral head more strongly than using low intensity pulsed ultrasound alone.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R681.8

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