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微泡增強(qiáng)超聲抑制激素性股骨頭壞死的動(dòng)物實(shí)驗(yàn)研究

發(fā)布時(shí)間:2018-08-14 09:23
【摘要】:背景:激素性股骨頭壞死是非創(chuàng)傷性股骨頭壞死中最常見(jiàn)的病因之一,目前尚沒(méi)有有效的手段來(lái)預(yù)防和治療激素性股骨頭壞死。已經(jīng)有動(dòng)物體內(nèi)實(shí)驗(yàn)研究證明低強(qiáng)度脈沖超聲可在一定程度上抑制激素性股骨頭壞死的進(jìn)展。我們?cè)诔暩深A(yù)的過(guò)程中加入微泡來(lái)驗(yàn)證微泡聯(lián)合低強(qiáng)度脈沖超聲是否可提高單純超聲干預(yù)對(duì)激素性股骨頭壞死的抑制作用。方法:兔子激素性股骨頭壞死的模型是通過(guò)一次低劑量?jī)?nèi)毒素聯(lián)合多次大劑量甲強(qiáng)龍注射來(lái)建立的。24只雄性新西蘭兔子(隨機(jī)平均分為三組,對(duì)照組(造模后不作治療),超聲組(造模后低強(qiáng)度脈沖超聲治療)和微泡超聲組(造模后微泡局部注射聯(lián)合低強(qiáng)度脈沖超聲治療)。低強(qiáng)度脈沖超聲的強(qiáng)度為200mW/cm2,每天治療20分鐘,共治療6周。6周后獲取雙側(cè)股骨頭標(biāo)本行micro-CT,生物力學(xué),實(shí)時(shí)定量PCR,western blot,組織學(xué)和免疫組織化學(xué)等檢測(cè)。結(jié)果:經(jīng)過(guò)6周的干預(yù)后,對(duì)照組中,骨密度,骨小梁數(shù)量,抗壓載荷和骨礦化率等顯著降低,表明我們的選模是成功的。微泡組中,骨密度值較超聲組顯著增高(932.6 ± 6.861 mg/cm2 vs.894.5 ± 12.84 mg/cm2),具有統(tǒng)計(jì)學(xué)差異(p0.001)。微泡組中,骨小梁數(shù)量較超聲組顯著增多(2.352 ± 0.06980/mm vs.2.213 ±0.07245/mm),具有統(tǒng)計(jì)學(xué)差異(p0.001)。骨小梁厚度在微泡組中較超聲組有所增厚,但無(wú)統(tǒng)計(jì)學(xué)差異(p=0.286)。微泡組中,骨礦化率顯著高于超聲組(2.660±0.2390μm/dayvs.1.913 ± 0.1457μm/day),具有統(tǒng)計(jì)學(xué)差異(p=0.008)。微泡組最大抗壓載荷值顯著高于超聲組(467.2 ± 65.96N vs.365.6 ±57.40N),且差異有統(tǒng)計(jì)學(xué)意義(P0.001)微泡超聲顯著增強(qiáng)了 FHN骨組織中VEGF和BMP-2的表達(dá)。微泡組血管數(shù)量明顯多于超聲組(13.7±4.3/mm2vs.8.3±1.6/mm2),差異有統(tǒng)計(jì)學(xué)意義(p=0.041)。微泡組的血管最小直徑大于超聲組(28.6 ± 4.6μm vs.23.9 ± 4.2μm),但是差異沒(méi)有統(tǒng)計(jì)學(xué)意義(p=0.205)。結(jié)論:我們的研究結(jié)果證實(shí),相比單純使用低強(qiáng)度脈沖超聲,微泡超聲對(duì)激素性股骨頭壞死進(jìn)展的抑制作用更強(qiáng)。
[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 鹵6.861 mg/cm2 vs.894.5 鹵12.84 mg/cm2). The number of bone trabeculae in microbubble group was significantly higher than that in ultrasound group (2.352 鹵0.06980/mm vs.2.213 鹵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 鹵0.2390 渭 m/dayvs.1.913 鹵0.1457 渭 m/day). The maximum compressive load in the microbubble group was significantly higher than that in the ultrasound group (467.2 鹵65.96N vs.365.6 鹵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 鹵4.3/mm2vs.8.3 鹵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 鹵4.6 渭 m vs.23.9 鹵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.
【學(xué)位授予單位】:浙江大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R681.8

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