【作者】 何仁荣；

【导师】 刘金文；

【作者基本信息】 广州中医药大学 ， 中医骨伤科学， 2007， 博士

【摘要】 恶性骨肿瘤总体发病率不高，但常造成病人肢体残疾甚至危及生命。近年来，手术、新辅助化疗等综合治疗方法的应用使恶性骨肿瘤的五年生存率大大提高，但中医药作为治疗恶性肿瘤综合治疗的一部分，其在稳定病灶、降低化放疗副作用、延长生存时间、改善生命质量等方面仍显示了独特的疗效和优势。由于各种原因条件的限制，中医药对恶性骨肿瘤的研究相对比较滞后，对其证候演变及病因病机还缺乏规律性的认识，中医药作用疗效及机理还有待实验研究的进一步验证和探讨。据此，本研究通过对MM临床回顾性调查研究探讨恶性骨肿瘤的中医证候及其病因病机特点，并对益气活血祛痰法干预恶性骨肿瘤作用机理进行实验研究。第一部分恶性骨肿瘤的证候调查目的：探讨恶性骨肿瘤患者的中医证候及其病因病机的特点，为科研及临床工作提供基础性研究。方法：采用回顾性调查研究方式，对MM中医证型的分布、中医证型与年龄、性别、临床分期、血红蛋白浓度和尿本周氏蛋白含量等相关因素进行统计分析。结果：1．MM各组证型之间有极显著性差异(P＜0.01)，以虚证(包括气虚证、血虚证)、血瘀证、痰(湿)证(包括痰浊证、湿热证和寒湿证)为主；2．60岁以下和60岁以上的MM患者所表现的中医证型没有显著性差异(P＞0.05)；3．男性和女性MM患者所表现的中医证型没有显著性差异(P＞0.05)；4．MM患者所表现的中医证型在不同临床分期间有极显著性差异(P＜0.01)；5．MM患者所表现的中医证型在不同血红蛋白浓度间有极显著性差异(P＜0.01)；6．MM患者所表现的中医证型在不同尿本周氏蛋白含量间有极显著性差异(P＜0.01)。结论：在MM中医证型中，气虚证、血虚证、血瘀证、痰(湿)证是MM的主要证型，虚、瘀、痰在MM的发病及发展中是主要因素；年龄、性别因素与MM的中医证型无关；临床分期、血红蛋白浓度、尿本周氏蛋白含量等因素与MM的中医证型密切相关。第二部分益气活血化痰法干预荷瘤小鼠的实验研究目的：探讨加味四物汤对恶性骨肿瘤体内浸润生长的生物学行为的影响及其机制。方法：建立KHOS成骨肉瘤原位移植模型，通过加味四物汤灌胃干预动物模型移植瘤的生物学行为，观察移植瘤的生长情况；通过RT-PCR方法定量检测移植瘤血管内皮细胞生长因子(VEGF)及其受体KDR和Flt-1的表达。结果：加味四物汤高剂量组有明显的抑瘤效果(P＜0.01)，中、低剂量组无明显抑瘤作用(P＞0.05)，加味四物汤高剂量组27.74％的抑瘤率高于中、低剂量组的3.98％、9.24％；加味四物汤高剂量组有明显抑制肿瘤组织VEGF、Flt-1、KDR表达的作用(P＜0.05)；中、低剂量组抑制肿瘤组织VEGF、Flt-1、KDR表达的作用不明显(P＞0.05)；中药高剂量组抑制肿瘤组织VEGF、Flt-1、KDR表达的作用优于中、低剂量组(P＜0.05)。结论：加味四物汤高剂量组可以抑制荷瘤小鼠体内肿瘤的生长，通过抑制VEGF、KDR、Flt-1的表达控制肿瘤新生血管的生长而达到阻止恶性骨肿瘤体内生长的目的。更多还原

【Abstract】 The total incidence rate of malignant bone tumor is low, but it oftenresults in extremity disability and even threat to life. For the past fewyears, five year survival rate consumedly raised since combined therapyincluding operation and neoadjuvant chemotherapy etc, was applied. TCM,as a part of combined therapy, manifests characteristic therapeuticeffect and potentiality on stabilizing the focus of infection, loweringchemoradiotherapy’s side effect, prolonging live time and improving thequality of life. On account of various kinds of reasons, the research onmalignant bone tumor by TCM is relatively lagging, the knowledge on theregular pattern of the development of its TCM syndromes and itspathogenesis is still insufficient, the curative effect and mechanism ofTCM demands to be authenticated further by empirical study. On thesegrounds, this study made a clinical retrospective study on malignant bonetumor patients to explore its Traditional Chinese Medicine (TCM)syndromes and the characteristics of its TCM pathogenesis, and madeexperimental study on the mechanism of action that the method ofinvigorating vital energy and promoting blood flow and eliminating phlegmto treat malignant bone tumor.PartⅠThe study on the changes of TCM syndromesof malignant bone tumor patientsAim:This study tries to find out the changes of TCM syndromes and thecharacteristics of TCM pathogenesis of malignant bone tumor patients,and hopes to provide fundamental research for clinical applications and scientific research.Method: statistical analysis on correlated factors including type ofTCM syndromes of MM, age, gender, clinical stage, hemoglobinconcentration, Bence Jones protein etc. was carried out by means ofretrospective review.Results:There are very significant differences among different TCMsyndrome types(P＜0.01). In the MM patients, most TCM syndromes aredeficient syndrome(including qi deficiency and blood deficiency), bloodstasis syndrome, phlegm-dampness syndrome(including phlegm-turbiditysyndrome, damp-heat syndrome and cold-damp syndrome). The TCM syndromeshave no significant differences between MM patients above 60 years oldand under 60 years old(P＞0.05). The TCM syndromes have no significantdifferences between male or female MMpatients (P＞0.05). The TCM syndromeshave significant discrepancy between different clinical stages of MMpatients (P＜0.01). The TCM syndromes have significant discrepancy betweendifferent hemoglobin concentration MM patients (P＜0.01). The TCMsyndromes have significant discrepancy between different Bence Jonesprotein MM patients (P＜0.01).Conclusion: Deficient syndrome (including qi deficiency and blooddeficiency), blood stasis syndrome, phlegm-dampness syndrome are the mainTCM syndromes of MM patients. Phlegm, stagnant blood and deficiencyinteract and get more and more heavy effect during the process of MM’soccurrence and development. The TCM syndromes of MM patients have nothingto do with gender and age. There are close relationships between TCMsyndromes of MM and clinical stage, hemoglobin concentration, Bence Jonesprotein.PartⅡEmpirical study on herbs of invigorating vital energy andpromoting blood flow and eliminating phlegm treating tumor-bearing miceAim: To investigate the effect and mechanism of modified Decoction ofFour Drugs on the biological behavior of the in vivo infiltrating growthof malignant bone tumor.Methods:We build the mice orthotropic transplantation model ofosteogenic sarcoma KHOS. Observe the growth of the transplantation tumorafter treating with the modified Decoction of Four Drugs by intragastricadministration to interfere the biological behavior of the animal models; measure the expression of VEGF, KDR, Flt-1 of the transplantation tumorby the way of RT-PCR method.Results:high-dose modified Decoction of Four Drugs group hassignificant effect on restraining the proliferation of bone tumorcells(P＜0.01), while middle and low-dose groups have no significant effecton restraining the proliferation of bone tumor cells(P＞0.05),thetumor-inhibiting rate of high-dose group is higher than that of the middleand low-dose groups which are 3.98% and 9.24% separately. The high-dosemodified Decoction of Four Drugs group has the effect of significantlyinhibiting the expression of VEGF, KDR and Flt-1 of the transplantationtumor tissue, while the effect of inhibiting the expression of VEGF, KDRand Flt-1 of the transplantation tumor tissue by the middle and low-dosegroups is not significant; the effect of the high-dose Chinese medicinegroup on inhibiting the expression of VEGF, KDR and Flt-1 of thetransplantation tumor tissue is better than that of the middle andlow-dose groups(P＜0.05).Conclusion: High-dose modified Decoction of Four Drugs group canrestrain the growth of bone tumor in vivo in tumor-bearing mice. Theinvasion of bone tumor can be depressed by reducing the expression ofVEGF, KDR and Flt-1 to control the growth of new vessels of tumor in orderto interrupt the in vivo growth of malignant bone tumor.更多还原