【作者】 樊效鸿；

【导师】 邓友章；

【作者基本信息】 成都中医药大学 ， 中医骨伤科学， 2009， 博士

【摘要】 【目的】探讨股骨头穿刺注射川芎嗪治疗激素诱导的兔股骨头坏死的修复效果和可行性,为进一步研究提供实验依据。评价股骨头穿刺注射川芎嗪对不同原因导致的股骨头坏死的治疗效果,为进一步临床推广提供依据。【方法】本实验分为两个部分。第一部分为动物实验,第二部分为临床观察。第一部分：激素诱导兔股骨头坏死模型的建立。成年新西兰大白兔48只,肌注醋酸泼尼松龙注射液8mg／kg／次,每周两次,共16次；同时注射青霉素钠和硫酸庆大霉素以预防感染,每次5万u／只。空白组在相同时间注射等量生理盐水。造模成功后,将实验动物分为4组。A组：空白对照组；B组：造模组；C组：股骨头穿刺组；D组：股骨头穿刺川芎嗪注射组。C组在造模成功后及第2、4、6周行股骨头穿刺。D组在造模成功后及第2、4、6周行股骨头穿刺川芎嗪注射。A组和B组不行股骨头穿刺和药物注射。治疗后第1、3、5、7周每组分别处死3只动物。取材进行组织形态学观察、组织形态学计量分析新骨生成、VEGF(血管内皮生长因子)免疫组化染色观察血管数量和血管面积图像分析。第二部分收集2002年1月至2007年1月间成都中医药大学附属医院骨科门诊股骨头坏死患者65例78髋。其中男38例(47髋),女27例(31髋)。年龄20～73岁,平均48.9岁。随访时间1.5年～6.5年,平均3.5年。每周行股骨头穿刺注射川芎嗪注射1次。四周为一个疗程,休息2月后再行下一个疗程,共治疗2～3个疗程。治疗期间同时进行辅助功能锻炼。定期随访,根据牛津髋关节评分系统进行临床疗效观察,根据ARCO分期分型系统进行影像学疗效观察。所有数据均采用SPSS11.5软件进行处理。【结果】动物实验结果①组织学：A组股骨头结构正常；B组造模成功后股骨头呈坏死表现,随时间推移无明显变化。C组经治疗后股骨头坏死表现有所改善。D组经治疗后股骨头坏死表现逐步改善,第7周时股骨头组织结构接近正常。②新骨生成面积：B组和C组没有差别(P>0.05),D组与B、C组在第5、7周时比较有统计学差异(P<0.05)。D组第5周和第7周比较有统计学差异(P<0.05)。③血管计数和血管面积：B组和C组各时段比较均无统计学意义(P>0.05)。D组和B、C组比较各时段均有明统计学差异(P<0.05)。D组各时段相比有统计学差异(P<0.05)。临床观察结果①临床疗效观察结果：优24.4%(19髋),良37.2%(29髋),可25.6%(20髋),差12.8%(10髋),总优良率61.6%；分期优良率：Ⅰ期72.7%(11髋),Ⅱ期67.6%(34髋),Ⅲ期56.0%(25髋),Ⅳ期37.5%(8髋)；分型优良率：A型73.1%(26髋),B型63.7%(22髋),C型57.1%(21髋)；②影像学疗效评价结果：优11.5%(9髋),良41.0%(32髋),可30.8%(24髋),差16.7%(13髋),总优良率52.6%(78髋)。分期优良率：Ⅰ期63.6%(11髋),Ⅱ期55.9%(34髋),Ⅲ期52.0%(25髋),Ⅳ期50.0%(8髋)；分型优良率：A型57.7%(26髋),B型59.1%(22髋),C型40.9%(22髋)。【结论】股骨头穿刺注射川芎嗪可以提高VEGF在血管内皮的阳性表达,促进局部血管增生,增加新骨形成,从而促进股骨头坏死的修复。股骨头穿刺川芎嗪注射可以明显改善股骨头坏死患者的髋关节功能,促进股骨头修复,防止或延缓坏死股骨头的塌陷,为其进一步临床应用提供了一定的理论依据。更多还原

【Abstract】 ObjectivesTo investigate the effectiveness and feasibility of treatments of rabbit femoral head necrosis induced by steroid injection using core decompression combined with injection of tetramethylpyrazine, and to provide the primary foundation for the further research. To evaluate the effectiveness of treatments of femoral head necrosis caused by different pathogeny using core decompression combined with injection of tetramethylpyrazine, and provides the primary datum for the further clinical application.MethodsThe study was divided into two parts. Part I was animal experiment, and part II was clinical study.Part I:The establishment of rabbit femoral head necrosis caused by steroid.48 adult New Zealand rabbits were injected with Prednisolone acetate 8mg/kg/time, twice one week,16 times totally. Penicillin and Gentamicin were injected meanwhile to prevent infection. Blank group was injected with equal dose of saline at the same time. The animals were divided into four groups after the successful induction. Group A: blank group. Group B:model group. Group C:core decompression group. Group D:core decompression combined with injection of tetramethylpyrazine. The animals in group C were managed with core decompression subtrochanterly at immediately after induction and 2、4、6 week. The animals in Group D were managed with core decompression plus injection of tetramethylpyrazine at the same time. Core decompression and injection of drug were not managed in animals in Group A and B. Three animals in all groups were sacrificed at 1、3、5 and 7 weeks after management. The femoral heads were prepared for observation of tectology, new formation of bone by computation analysis, blood vessels account and area by immunity histochemistry with VEGF.Part II:Collecting 65 patients with 78 hips of femoral head necrosis from 2002 January 2002 to January 2007 in Orthopedic Department of accessory hospital of Chengdu University of Tradition Chinese Medicine.38 patients with 47 hips were male and 27 patients with 31 hips were females. The average age were 48.9 ranged from 20 to 73. The mean following-up was 3.5 years ranged from 1.5 to 6.5 years. The patients were managed with core decompression subtrochanterly and injection of tetramethylpyrazine every week.4 week was a period of treatment, and the next period of treatment started after two months rest. Generally the patients received 2～3 periods of treatment. The assistant function exercise was carried out at during the treatment. Clinical effectiveness was observed periodically with Oxford Hip Joints Evaluation System, and radiology effectiveness with ARCO Stage and Type System.All datum were dealt with SPSS11.5 statistical software.ResultsAnimal study results①Histology:The structure of Group A femoral head was normal. Necrosis was found in Group B femoral head, and there was no changes with time elapsed. In Group C, the necrosis of femoral head was ameliorated after core decompression. The necrosis of femoral head in Group D was ameliorated gradually, and the structure of femoral head was nearly normal at 7 week after treatment.②The area of new bone formation:There was no significant difference between Group A and Group B (P>0.05),and there was significant difference between Group D and Group B and C (P<0.05) there was significant difference in Group D at time 5 week and 7 week (P<0.05).③Blood vessels and area:There was no significant difference between Group B and C at all times (P>0.05).There was significant difference between Group D and Group B and C at all times (P<0.05).There was significant difference in Group D at all times (P<0.05)Clinical observation results①Clinical effectiveness results: excellent 24.4%(19hips), good 37.2%(29 hips), moderate 25.6% (20 hips), unacceptable 12.8%(10hips), total choiceness rate 61.6%; By stages choiceness rate:stageⅠ72.7%(11 hips), stageⅡ67.6%(34 hips), stageⅢ56.0%(25 hips), stageⅣ37.5% (8hips); By types choiceness rate:type A73.1%(26 hips), type B 63.7%(22 hips), type C 57.1%(21hips);②Radiology effectiveness results:excellent 11.5%(9 hips), good 41.0%(32hips), moderate 30.8%(24hips), unacceptable16.7%(13 hips), total choiceness rate 52.6%(70 hips)。By stages choiceness rate:stageⅠ63.6%(11 hips), stageⅡ55.9%(34 hips), stageⅢ52.0%(25 hips), stageⅣ50.0% (8v); By types choiceness:type A 57.7%(26 hips), type B 59.1% (22 hips), type C40.9%(22 hips)ConclusionsCore decompression combined with injection of etramethylpyrazine can increase the positive expression of VEGF in endothelium, promote the formation of blood vessels and new bone, by which mechanism the femoral head was repaired. Core decompression combined with injection of etramethylpyrazine can improve the function of hips significantly in femoral head necrosis patients, and promote the repair of femoral head, prevent the dent of femoral head or delay the process of dent, which provides the theoretical foundation for further clinical application in some extent.更多还原