中药配合髓芯减压术治疗激素性股骨头坏死的临床及实验研究

【作者】 李德魁；

【导师】 徐林；

【作者基本信息】 北京中医药大学 ， 中西医结合骨科， 2008， 博士

【摘要】 激素性股骨头坏死属难治疾病,发病率和致残率高,严重影响患者的生活质量。但激素性股骨头坏死确切的发病机制尚未十分清楚,限制了预防和治疗工作的开展。手术是遏制激素性股骨头坏死进程和防止塌陷的基本方法和前提,但有其自身的局限性。中医药治疗激素性股骨头坏死有着显著优势,疗效满意,但单纯中医治疗也存在不足。探讨如何将西医手术和中医药的治疗优势有机结合,寻求一种疗效确切,费用低廉,副作用少的综合疗法,对于提高治疗激素性股骨头缺血性坏死的疗效,减轻患者和社会经济负担具有重要意义。1.目的:以激素性股骨头坏死为研究对象,通过文献分析、实验研究和临床观察,对中西医治疗SANFH的结合点进行探讨,以期建立治疗SANFH的独特指导原则,为临床选择合适的治疗方案、合理用药,提供新的思路。2.方法:2.1理论研究:采用文献学、逻辑分析等方法,对中、西医对激素性股骨头坏死病因病机的各自认识、治疗现状及前期的实验结果进行阐释和分析,提出中西医结合治疗激素性股骨头坏死的可行性思路和途径,并对其二者的结合点进行探讨。2.2临床研究:(1)总体思路:SANFH的治疗一直是医学界的难点,手术是遏制SANFH进程和防止塌陷的基本方法和前提,但有其自身的局限性。中医药治疗SANFH有着双向调节作用,但是单纯中医治疗也存在不足。本研究课题所在单位已经在骨坏死的中西医结合治疗领域进行了全面扎实的前期探索性基础和临床研究工作。从2003年起,对激素性股骨头坏死患者进行了髓芯减压术,同时配合口服木豆叶与中医康复治疗,取得了良好的治疗效果。本研究通过对近年来综合疗法治疗激素性股骨头坏死的病历进行回顾分析,以完成中药配合髓芯减压术治疗SANFH的疗效评估,并在此基础上总结治疗经验和规律,以指导进一步临床应用和研究。(2)一般资料:以激素性股骨头坏死病人为观察对象,按照诊断标准,纳入标准及排除标准,选择2003年-2006年东直门医院激素性股骨头坏死患者共58例。(3)调查指标:一般项目包括患者姓名、性别、年龄、职业、入院明确诊断、治疗方案等。调查项目包括肾功能指标、生化指标、效性指标、影像学指标及综合临床疗效评定指标。(4)统计方法:运用SPSS13.0分析软件进行T检验和单因素方差分析。2.3实验研究:(1)总体设计:本实验研究主要以建立与人类SANFH有相似性和可比性、符合人类SANFH病变的客观规律、经济可行的动物模型为切入点,选择了与激素性股骨头坏死密切相关的VEGF及相关细胞因子作为研究的对象。观察在激素冲击下,所观测指标(组织形态、VEGF、BMP-2)在采用不同治法下治疗前后的变化,并对其相关性进行了比较分析。(2)实验动物:健康新西兰大耳兔,雄性,4周龄,体重0.60±0.11kg。将所用新西兰大耳兔置入特制的笼中,自然光照,自由摄取食水,室温饲养。造成直立行走兔模型;参照贺氏造模法,肌注醋酸泼尼松龙8mg/kg/次,每周两次,连续注射8w。造模成功后,经影像学检查,参照国际ARCO分期标准进行分期。随机分组后,进行中药、手术及综合治疗。(3)检测方法:病理组织学检查,运用光镜、电镜观察;动态血清中BMP-2测定,运用放射免疫法。VEGF和BMP-2测定,运用免疫组化法;(4)分析方法:所有数据以(?)±SE表示,组间差异利用SPSS13.0统计软件包进行ANOVA检验,以P＜0.05差异为有显著性。变量关系采用直线相关分析。3.结果:3.1理论研究结果:激素性股骨头坏死属临床难治疾病,发病率和致残率高,严重影响人们的生活质量。但激素性股骨头坏死确切的发病机制尚未十分清楚,限制了临床预防和治疗工作的开展。手术是遏制激素性股骨头坏死进程和防止塌陷的基本方法和前提,但有其自身的局限性。中医药治疗激素性股骨头坏死有着显著优势,但单纯中医治疗也存在不足。要创立治疗激素性股骨头坏死的独特指导原则,关键在中西医治疗激素性股骨头坏死的结合点的确定。或许通过西医的手段,创造有利于股骨头坏死组织修复的局部环境,再加上中医药的促进作用,能达到事半功倍的效果。股骨头坏死的动物模型对探索成功的治疗模式是必不可少的,新的治疗方法的探索因缺乏与人股骨头坏死相一致的动物模型而受阻碍。如何制造出更符合人类股骨头坏死发展的动物模型,是一个迫切需要解决的问题。3.2临床研究结果:3.2.1治疗前后Harris评分变化Harris评分显示:中药组临床治愈9髋,显效2髋,有效4髋,无效7髋;手术组临床治愈3髋,显效3髋,有效9髋,无效5髋;综合组临床治愈11髋,显效5髋,有效4髋,无效5髋。3.2.2三组影像学疗效比较影像学指标:中药组显效8髋,有效8髋,无效6髋;手术组影像学指标显效10髋,有效4髋,无效6髋;综合组影像学指标显效13髋,有效6髋,无效3髋。3.2.3三组总疗效比较综合临床疗效评定显示:中药组显效8髋,有效8髋,无效6髋,总有效率72.72%;手术组显效6髋,有效9髋,无效5髋。总有效率75.00%;综合组显效11髋,有效11髋,无效3髋。总有效率88.00%。3.3实验研究结果3.3.1 VEGF表达水平:模型组VEGF表达水平在第二周时较空白组升高,但第四、八周VEGF表达水平逐渐降低,明显低于空白组。3.3.2血清BMP-2含量:模型组血清BMP-2含量较空白组降低,其差异有显著性(P＜0.01)。3.3.3中药组、手术组和综合组BMP-2水平均较模型组升高,有显著性差异(P＜0.01),说明三者均能通过升高BMP-2水平来治疗激素性INFH;中药组、手术组和综合组比较而言,综合组BMP-2水平升高最为明显,和其他两组相比有显著性差异。中药组BMP-2水平稍高于手术组,但二者相比,其差异无统计学意义。4.结论:4.1激素很可能是通过抑制VEGF的表达而使股骨头缺血性坏死的血管无法再生,减少血供,导致骨细胞死亡,继而发生股骨头缺血性坏死。4.2 BMP-2水平降低可能是激素性INFH发生的因素之一。4.3中药配合髓苍减压术治疗是治疗激素性股骨头坏死的最佳选择。更多还原

【Abstract】 Steroid-induced Avascular Necrosis of the Femoral Head（SANFH）is a kind of refractoriness disease,whose attack rate and mutilation rate are very high,which seriously affect patient’s living quality.But the exact nosogenesis of SANFH is not fully understanded.Which restrict the development of prophylaxis and cure method.Operation is the basic method and premise,but operation is also local.Traditional Chinese medicine has notable superiority to cure SANFH,it’s curative effect is content.But cure method only by TCM also has it’s insufficiency. To study how to combine operation and TCM,seek a combined therapy which has certain curative effect,low cost and few side effect,is important to raise cure effect of SANFH, economics burden of patient and society lessen.1 ObjectiveBy literature analysis,empirical study and clinical observation,to study the cure SANFH method by combining site of modern and TCM,expect to found the guide principle of cure SANFH,provide new method for clinical select suitable treatment plan and rational use.2 Method2.1 Theory researchBy method of bibliography and logic analysis,explain and analysis each recognition to etiological and pathogeny,cure status quo of SANFH and prophase experiment result,provide think method and way to cure SANFH by combination of TCM with Western medicine,and study the combining site.2.2 clinical research（1）overall thinking route:SANFH treatment has been the medical arena difficulty,surgery is the essential method and premise contains the SANFH advancement and prevents the collapse, but has its own limitation.Chinese medicine has the bidirectional control action to SANFH treat, but the pure Chinese medicine treatment also has the insufficiency.This research subject had already carried on the comprehensive solid preliminary exploring foundation and the clinical research work in the osteonecrosis cooperation of Chinese and Western medicine treatment domain.From 2003,has carried on the Core Decompression technique to the Steroid-induced Avascular Necrosis of the Femoral Head patient,simultaneously coordinated the Mu Dou leaf and the Chinese medicine recovery treatment,has obtained the good treatment result.This research through carring on the review analysis to the recent years composite treatment Steroid-induced Avascular Necrosis of the Femoral Head’s medical record,completed the traditional Chinese medicine coordination Core Decompression technique to treat SANFH the curative effect appraisal,based on this and summarized the treatment experience and the rule, instructed further clinical practice and research..（2）common material:Take the Steroid-induced Avascular Necrosis of the Femoral Head patient as the object of observation,according to the diagnosis standard,integrates the standard and the elimination standard,chose 2003-2006 Steroid-induced Avascular Necrosis of the Femoral Head patient altogether 58 examples of the Dongzhimen hospital.（3）investigates the target:Generally the project including the patient name,the sex,the age, the occupation,is hospitalized to be clear about the diagnosis,the therapeutic schedule and so on.Investigation project including kidney function target,biochemistry target,effect target, phantom study target and synthesis clinical curative effect deliberated index（4）statistical method:Carries on the T-test and the single factor variance analysis using the SPSS 13.0 analysis software.2.3 Experimental studies: （1）General layout:This experimental study mainly take establishes with human SANFH has the similarity and the commeasurability,conforms to the human SANFH pathological change’s objective law,the economical feasible animal model as a breakthrough point,has chosen takes the research with Steroid-induced Avascular Necrosis of the Femoral Head close related VEGF and the correlation cell factor the object.Around the observation under the hormone impact, observes the target（organization shape,VEGF,BMP-2）change that before and after using different treat law,and has carried on the comparative analysis to its relevance.（2）Animal experimental:Health New Zealand big ear rabbit,male gender,4 week age,body weight 0.60±0.11kg.New Zealand big ear rabbit will be post specially made cage,the natural illumination,the freedom absorbs the drinking water,room temperature raising.Refers to He’s making mold law,intermuscular injection acetic acid Prednisone dragon 8mg/kg/time,two times every week,injects 8w continuously.After making the mold success,after the phantom study inspection,reference international the ARCO standard carries on by stages by stages. After stochastic grouping,carries on the traditional Chinese medicine,the surgery and the complex therapy.3)Examination method:The histo-pathology inspection,utilizes the light microscope,the electron microscope observation;VEGF determination,utilization immunity group reduction; Blood serum BMP-2 determination,utilization emission immunization technology.（4）Analysis method:All data by^?±SE the expression,the group difference carry on the ANOVA examination that using the SPSS13.0 statistics software package,The difference has the significance by P＜0.05.The variable relations use the straight line correlation analysis.3.Result:3.1 Fundamental research resultSteroid-induced Avascular Necrosis of the Femoral Head is clinical difficult to be treated disease, the disease incidence rate and crippling rate is very high,serious influence people’s life quality. But the Steroid-induced Avascular Necrosis of the Femoral Head accurate pathogenesis was not yet clear,this limit the clinical prevention and the treatment work development.Surgery is contains the h Steroid-induced Avascular Necrosis of the Femoral Head advancement and prevents the collapse the essential method and the premise,but has its own limitation.Chinese medicine treatment Steroid-induced Avascular Necrosis of the Femoral Head has the remarkable superiority,but the pure Chinese medicine treatment also has the insufficiency.The unique guiding principle treatment Steroid-induced Avascular Necrosis of the Femoral Head’s must be establish,the key treat Must establish’s combining site determination in the doctor practicing between Chinese medicine and western medicine.Through doctor western medicine’s method practicing,Creation advantageous that perhaps is the local environment which organizes to be repaired,in addition Chinese medicine promoter action,can achieve the twice result with half the effort effect.The animal model to explores the successful treatment pattern is essential,the new method of treatment’s exploration because of lacks receives with the annual bonus bone necrosis consistent animal model hinders.How to make conforms to the animal model which human Must establish develops,is a question which urgent needs to be solved.3.2 Clinical research results:3.2.1 Harris grading changes prior-treatment and post-treatmentThe Harris grading to demonstrate:The traditional Chinese medicine group clinical cures 9 hips,excellent results 2 hips,effective 4 hips,invalid 7 hips;The surgery group clinical cures 3 hips,excellent results 3 hips,effective 9 hips,invalid 5 hips;The comprehensive group clinical cures 11 hips,excellent results 5 hips,effective 4 hips,invalid 5 hips. 3.2.2 Three group of imaging study curative effects compare the phantom study target: The traditional Chinese medicine group shows results 8 hips,effective 8 hips,invalid 6 hips; The surgery group phantom study target shows results 10 hips,effective 4 hips,invalid 6 hips; The comprehensive group phantom study target shows results 13 hips,effective 6 hips,invalid 3 hips.3.2.3Three groups of total curative effects compare demonstrate:The traditional Chinese medicine group shows results 8 hips,effective 8 hips,invalid 6 hips, total effectiveness 72.72%;The surgery group shows results 6 hips,effective 9 hips,invalid 5 hips.Total effectiveness 75.00%;the synthesis group shows results 11 hips,effective 11 hips, invalid 3 hips.Total effectiveness 88.00%.3.3 Experimental study result3.3.1 VEGF expression level:Model group VEGF expression level compares the blank group elevate after the second week,but the fourth,eighth week VEGF expression level reduces gradually,lower the blank group obviously.3.3.2 BMP-2 content:The model group blood serum BMP-2 content compares the blank group to reduce,its difference has the significance（P＜0.01）.3.3.3 Traditional Chinese medicine groups,the surgery group and the synthesis group BMP-2 water elevate mean difference to model group,has the significance difference（P＜0.01）. Explained that three can through elevate the BMP-2 level to treat hormone nature INFH;the comprehensive group BMP-2 level elevates obviously,compares with other two groups has the significance difference.The traditional Chinese medicine group BMP-2 level is higher than the surgery group slightly,but the two compare,its difference non-statistics significance.4 Conclusion:4.1 Hormone make avascular necrosis of the femoral head’s blood vessel has no way to regenerate might by restraint VEGF express,reduce blood supply,result in osteocyte death,and continue make avascular necrosis of the femoral head.4.2 BMP-2 level cut down might be one of the factors of SANFH.4.3 Traditional Chinese medicine coordination Core Decompression technique to treat SANFH is the best method to treat Steroid-induced Avascular Necrosis of the Femoral Head.更多还原